2017 Volume II
Wilmot Cancer Institute | University of Rochester Medical Center
Science at the Bedside Nurse researchers tackle complex clinical questions p. 8
Le tt e r f rom t h e Di re ct or Hello Friends of Wilmot Cancer Institute,
Jonathan W. Friedberg, M.D., M.M.Sc. Director, Wilmot Cancer Institute
For many patients and families, nurses are the first and primary contact at Wilmot Cancer Institute. Across the Rochester and Finger Lakes region, we have over 300 nurses who work in infusion centers, medical and radiation oncology clinics, and on our inpatient units. They are indispensable members of our team, guiding patients through complicated, high-stress situations and serving as critical links for physicians. They are dedicated to those they care for and those they work with. Above all else, our nurses bring compassion and commitment to helping patients and families navigate the most challenging times of life. What you may not realize is that they are also important members of our research team — seeking evidence-based strategies to improve the way we deliver care. With daily experience on the front lines, nurses bring a different perspective to cancer research. They’re trained to address acute problems, to be nimble and quickly identify important clinical issues. Not only do they understand biology, they understand how our care teams interact and the impact of external pressures on patients in their care. In this edition of Dialogue, you’ll read about three teams of nurses tackling questions about patient acuity, fall prevention and symptom management. Advances in cancer care come only from research, and our nurses are key members of these efforts. Their focus on patient experience and quality of life makes them ideal investigators. As with scientists who work in our labs, our nurse researchers are methodical in designing their studies and in gathering and analyzing their data. Their work is critical to the experience of our patients and to the approaches that we take in our clinics and units. They are helping us build a nursing research program at Wilmot in conjunction with the University of Rochester School of Nursing. Their findings — like those of our scientists and clinical researchers — have an impact far beyond our region as they are presented at national meetings and published in respected journals. I’m proud of the work they do — with our patients and with their research — and I’m honored to work with this incredible, talented team.
Jonathan W. Friedberg, M.D., M.M.Sc.
On the Cover
Sara Luzunaris, B.S., R.N., and Shannon O’Leary, B.S.N., R.N., O.C.N., are among the nurses at Wilmot who conduct research to address clinical issues and improve care. Cover photo: Matt Wittmeyer The Wilmot Cancer Institute is a component of Strong Memorial Hospital.
Wilmot Cancer Institute National Advisory Board Members 2017 Dennis Wilmot, Chair Dick Bell Elaine Bucci Michael Buckley Rina Chessin Michael Crumb Patrick Cunningham James Hammer Robert Kessler Kathy Landers Michael Linehan Alyssa Lozipone Jett Mehta Carol Mullin Walter Parkes Barbara Pluta-Randall Mary Pluta Ronald Pluta
Donald Rhoda Steve Whitman Paul Wilmot Richard Yates Keith Yeates John Zicari Faculty Members Yuhchyau Chen, M.D., Ph.D. Jonathan W. Friedberg, M.D., M.M.Sc. Aram F. Hezel, M.D. Hucky Land, Ph.D. David C. Linehan, M.D. Christian Peyre, M.D. Gary Morrow, Ph.D., M.S. Emeritus Members Judy Linehan Jim Ryan, Jr.
Ex-Officio Members Kellie Anderson Jonathan W. Friedberg, M.D., M.M.Sc. Hucky Land, Ph.D. David C. Linehan, M.D. Kristie Robertson-Coyne Mark Taubman, M.D. Honorary Board Members Dr. George Abraham Elaine Del Monte Richard DiMarzo Michael Donnelly Joan Feinbloom Janet Felosky Paul Hanrahan Gary Haseley Mark Kokanovich Frank and Cricket Luellen Sandra Hawks Lloyd Ronald Maggio
Steve McCluski Michael Norris Jeff Pierce Larry Rabinowitz Gregory Smith David Vigren Philip Wehrheim Timothy Williams Timothy Wilmot Thomas and Colleen Wilmot Bruce Zicari, II
Dialogue Editor / Writer Lydia Fernandez, Senior Public Relations Associate (585) 276-5788 Contributing Writers Ruth Harper-Rhode Leslie Orr Art Director / Designer Heather Deal Feature Photography Matt Wittmeyer
CONTENTS COVER STORY
Bringing the Bench to the Bedside Nurses at Wilmot Cancer Institute take a scientific approach to resolving urgent clinical problems and investigating new tools to manage care. The patient below is participating in a nurse-designed research study.
2017 Volume II
4 Finding Cancer’s Fingerprint The Molecular Genetic Pathology team uses a cancer’s mutational profile to help clarify diagnosis and inform treatment plans.
16 An Inside Look A translational brain mapping program brings new science into surgical practice and improves precision for the removal of brain tumors.
23 Committed to Research The Cadregari family shares what motivated them to support lymphoma research at Wilmot Cancer Institute.
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Community Focus
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News Briefs
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“Bubbles” Boost Search for Treatment to Aid Head and Neck Cancer Patients By Leslie Orr
Catherine Ovitt, Ph.D., Danielle Benoit, Ph.D., and Lisa A. DeLouise, Ph.D., are working to find new treatments to prevent damage to salivary glands during radiation.
A scientific team at the University of Rochester is using innovative technology to discover preventative treatments for salivary gland radiation damage typical for head and neck cancer patients—and recently received a $3.8 million National Institutes of Health grant to support their investigation. Cancer patients can lose salivary gland function during treatment for head and neck tumors. The irreversible damage, which prevents patients from producing saliva, often results in permanent dry mouth and makes it difficult to eat, speak, and swallow. The team will develop salivary gland tissues using a unique chip technology called “microbubbles,” which are tiny spherical wells or bubbles that can hold cells. The use of the microbubble platform is
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based on several years of salivary gland research, led by Catherine E. Ovitt, Ph.D., associate professor of Biomedical Genetics, a member of the UR Center for Oral Biology, and an expert in the repair and regeneration of salivary glands, and Danielle Benoit, Ph.D., associate professor of Biomedical Engineering and an expert in drug delivery systems and hydrogel platforms for tissue engineering approaches. Together with Lisa A. DeLouise, Ph.D., associate professor of Dermatology and Biomedical Engineering, who developed and received several patents for the microbubble concept, the scientists are working as co-principal investigators on the NIH project. Their goal is to find drugs that could be given to patients prior to radiation treatment that would prevent damage to
the glands. “Dr. Ovitt and I have shown through years of investigation that being able to develop functional salivary gland tissue for testing is the key to solving this problem,” Benoit says. “So, it’s microbubbles to the rescue.” Expanding cells and tissue outside of the body is elusive. In this case the process involves taking salivary gland cells that have been removed from humans undergoing surgery, expanding the cells, and studying their reaction to various drugs. A major problem, however, starts to occur as soon as the tissue is removed from the body and isolated: Cells immediately begin to lose their natural function. In the body, cells send signals and secrete proteins that are essential for their survival. In a culture plate in a laboratory, however,
these signals and proteins are diluted and dispersed, making the cells no longer viable. DeLouise’s technology at first glance looks similar to a cell culture petri dish, a round piece of silicone about the size of the large cookie. But within the dish are an arrangement of thousands of tiny round “micro-wells,” each one comprising a minuscule compartment for cell growth and tissue formation. The unique shape of each microbubble creates a niche that concentrates the cells, allowing them to proliferate and form salivary gland units. The microbubbles come in different sizes, and the beauty of the technology is that scientists can grow cells in thousands of bubbles at one time. DeLouise can make dishes the size of a dime that include more than 5,000 microbubbles. In addition,
Benoit’s lab has produced hydrogel materials that can be placed inside each microbubble that further allow the cell to maintain its structure and function. If the team can successfully grow human salivary gland cells in the microbubbles, they say, they will also be able to rapidly test thousands of existing Food and Drug Administration-approved drugs on the salivary tissue using the microbubble technology. “Only one treatment is currently available for radioprotection but it comes with many side effects, so most patients discontinue it,” Ovitt says. “There is a great need for additional ways to either cure or prevent this debilitating condition.” The team is collaborating with Shawn D. Newlands, M.D., Ph.D., M.B.A., chair of the
Department of Otolaryngology and member of the Wilmot Cancer Institute’s head and neck oncology team, to collect salivary tissue from consenting patients undergoing salivary gland surgery. Salivary gland cells are isolated from these tissues for seeding into microbubbles for the investigation. Additionally, Paul Dunman, Ph.D., associate professor of Microbiology and Immunology, will provide high-throughput drug-screening expertise during the second phase of the project, which is contingent upon successful development of the human gland chips.
In dishes the size of a dime, scientists can use microbubbles to grow thousands of cells.
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By Lydia Fernandez
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In cancer, pathology plays a key role in determining treatment options. Using a microscope to examine cells and tissue collected from a biopsy, pathologists can identify what type of cancer a patient has and its stage. For decades, that was enough information for oncologists to predict the likely course of the disease and to plan treatment. As science has advanced, however, cancer’s molecular make-up — DNA, RNA, proteins and other features — has become an increasingly important factor. It provides a fingerprint that offers additional clues to prognosis and which therapies will be most effective. This fingerprint, or mutational profile, can also serve as a marker for following the disease and its changes over time. It can be as important an indicator for beginning cancer treatment as it is for identifying remission and ending treatment. The challenge is that scientists, pathologists and oncologists are still discovering mutations that drive cancer and therapies that will target them. “No two cancers are the same,” explains Yi Ding, M.D., Ph.D., associate director of UR Medicine’s Molecular Genetic Pathology Unit. “Each delivers customized mutations that cannot be fully anticipated. It’s like a puzzle, and we’re trying to put all the pieces together.” Ding and her team are keeping Wilmot Cancer Institute at this leading edge of precision medicine. Working closely with Wilmot’s clinicians, they are developing new tests to identify the genetic and molecular features of different cancers. Their work is essential to clarifying diagnosis and informing treatment plans, especially with complex cases. Not only can they help oncologists identify targeted therapies or clinical trials that address those features, they are also a starting point for monitoring minimal residual disease for clinical and research questions. In the following conversation, Ding explains more about how molecular genetic pathology is changing the way we understand and treat cancer.
Yi Ding, M.D., Ph.D., is the associate director of UR Medicine’s Molecular Genetic Pathology Unit. As medicine and technology becomes more complex, pathologists are essential to precision care.
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Todd Laughlin, a pathology technical specialist, prepares to run a sample through the next-generation sequencing machine.
What can you learn from looking at a cancer’s mutational profile? Quite a lot, actually. The cancer’s mutational profile is like its fingerprint, and we’re trying to find it as early as possible. It has implications for diagnosis, prognosis and treatment. For example, using tools called genomic sequencing assays, we can identify the genetic variations in all of a cancer’s cells. These variations can serve as indicators for which therapies might be most effective. This can be especially helpful for patients with metastatic cancer or cancer that does not respond to standard treatment. By looking at their mutational profile, we can identify features that make the patients eligible for clinical trials testing new targeted therapies. These assays can also help us identify the tissue of origin for a cancer of unknown primary, a rare condition in which cancer cells are present in the body but the place where they began is not known. For some types of cancer, especially in their earlier stages, a patient may not need
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to be treated right away with targeted treatment and watchful waiting after management like surgery may be appropriate. In these cases, the mutations identified by molecular diagnostic assays serve as biomarkers that we can follow as we track the patient’s disease. Traditionally, we would track the patient by watching for clinical symptoms, but when they show up, it can be too late. This gives us an opportunity for early intervention. Can you look at the molecular profiles of all cancers? Like the Human Genome Project that was completed in 2003, a human cancer blueprint would be another incredible voyage of discovery. Because we don’t yet know the clinical significance of every mutation and because genomic sequencing is still very expensive, this kind of testing is not done for all cancers. Scientists and clinical investigators continue to study cancer’s genome, and eventually this kind of testing may become routine for every patient. For now, we focus on the gene variants
that have the most impact on clinical care. We are trying to find targets we can act on — molecular features that make the cancer susceptible to specifically designed therapies. We are also looking for variants that predict sensitivity, resistance or toxicity to a specific therapy; that influence disease prognosis; or that serve as inclusion criteria for clinical trials. With non small-cell lung cancer, for example, we look for molecular features such as mutations to the EGFR, KRAS, BRAF, ALK and ROS1 genes, or the presence of proteins such as PD1 or PD-L1. These genes and proteins are involved with mechanisms that encourage cancer’s growth, but they also have therapies specifically designed to target and interrupt them. How do you see a cancer’s molecular features and how do you know what to look for? We can’t actually look at a cancer’s molecular features the way we can look at cancer cells under a microscope. Instead, we take a very small sample of tissue from
a biopsy and run it through a machine that does next-generation sequencing, or NGS. Sequencing identifies the order of bases — called A, C, T and G, for short — in a strand of DNA. A next-generation sequencing machine can analyze the bases in millions of DNA strands simultaneously, and it gives us a report of every DNA sequence in the tissue. This data can help us at an unprecedented level refine diagnosis and prognosis, and predict drug responses and the efficacy of treatments. It also enables us to evaluate disease susceptibility and monitor disease progression.
evidence of lymphoma, and we needed to know whether it was related to the lymphoma in the GI tract. If it was related, that would have important implications for treatment planning. Using our clonality test, we were able to confirm that they were unrelated lymphomas, and the patient’s treatment plans could remain the same. Tests like this are incredibly important in guiding how aggressive therapy should be and avoiding unnecessary treatment.
What if you don’t have a test available for the molecular feature you want to examine?
Molecular oncology is extremely complex, and we are still learning how to link molecular targets to cellular pathways involved in a cancer’s growth and survival. There are also challenges associated with tumor heterogeneity and the potential limitations of a single biopsy. Tumor cells can have different profiles even within the same tumor, and different sites of metastases can have different tumor subclones and mutations. Also, treating tumors with cytotoxic therapies such as chemotherapy before sequencing can often increase instability and alterations within a cancer’s genome, complicating our ability to determine tumor evolution and heterogeneity. As more and more data come through genomic sequencing, there are other barriers for translating this into clinical practice, including cost-effectiveness and the ability to turn results around quickly.
We work very closely with the oncologists at Wilmot Cancer Institute, and we are constantly working on expanding our test menu to meet clinical needs. If we don’t have a test they want, we develop one. Since 2016, our lab has focused on NGS and the development of clinical applications. All of our clinical molecular diagnostic tests are laboratory-designed tests, meaning they are designed, manufactured and used within our laboratory. Our lab is Clinical Laboratory Improvement Amendments (CLIA) certified, and it is accredited by the New York state Department of Health and the College of American Pathologists. Recently, we developed a test for clonality — the first one designed and approved in New York state — which can help us figure out whether cancers in different parts of the body are derived from the same cells. This is especially helpful with lymphoma. We recently had a case with a patient who, based on symptoms and a biopsy from the gastrointestinal tract, was diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma. The patient had also undergone a bone marrow biopsy as part of testing to determine the stage of the cancer. The bone marrow biopsy also showed
What are the biggest challenges in this field?
How has this technology changed the role of pathologists in cancer? Medicine has transformed at a dizzying pace over the last decade, much of it fueled by rapid advances in genomics and technology like NGS. As this technology becomes more widely available, pathologists will need to work more closely with clinicians to interpret and integrate these test results as part of an overall diagnostic work-up.
John Fitzsimmons extracts DNA from a blood sample for molecular testing.
Understanding whether and how a gene plays a key role in the development of a cancer is important. For example, in lung cancer, adenocarcinoma (also called non-small cell lung cancer) and small cell lung cancer are biologically distinct. They both, however, can have a mutation of the EGFR gene. That mutation can make the lung adenocarcinoma more sensitive to a targeted therapy, but it may not have such benefit in the small cell lung cancer, in which further study of the genetic characteristics of such mutations is still needed. Similarly, a mutation of the BRAF V600E gene may predict sensitivity to a targeted therapy called a monoclonal antibody for melanoma. In contrast, that same mutation negates the benefit of that monoclonal antibody in colorectal cancers that have wild-type KRAS mutations. Furthermore, the presence of a mutation or other ayptical molecular results may not necessarily be an indicator of malignancy. The complexity is amazing. In the molecular era, pathologists will be critical in guiding clinicians on how to interpret molecular findings, and together, they will be central to the effort of precision medicine.
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COVER STORY
By Leslie Orr
The seventh floor of the Wilmot Cancer Center, with its panoramic views and 31 private, light-filled hospital rooms, hums with a calmness that contradicts the reality of life-threatening emergencies that can take place at any minute. Nearly every room is filled with people whose conditions can fluctuate by the hour; 55 skilled nurses monitor and care for them with compassion during high-risk treatments and for serious complications from cancer or the therapy they received. WCC7 is also the research “bench” for investigations to improve patient care and nursing practice. The up-and-coming research champions on the unit, Sara Luzunaris, B.S., R.N., a WCC7 nurse manager who’s been a nurse for eight years, and Shannon O’Leary, B.S.N., R.N., OCN, an assistant nurse manager who’s been a nurse for five years— proudly call themselves “the research nerds.” “We’re determined to get past the theory that, ‘We’ve always done things this way,’ ” Luzunaris says. “Nursing in general is becoming evidence-based in nearly every way and this means taking into account not only clinical experience and patient desires, but the current findings from data and the literature.” Their data helps to manage the intensity of taking care of very sick patients. Recently O’Leary led a project known as the acuity study, which was presented at this year’s national Oncology Nursing Society’s annual meeting. The goal was to capture in detail and with precise accuracy the level of sickness for each patient on WCC7, improving the ability to assign a proper nurse-to-patient ratio.
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Sara Luzunaris, B.S., R.N., and Shannon O’Leary, B.S.N., R.N., OCN, are leading data-driven nursing on WCC7.
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COVER STORY
When patients arrive they’re usually assessed in standard ways: by their vital signs, medications, and the professional but subjective judgment of a nurse. O’Leary wondered if the standard method was accurate enough. As part of a nursing practice research internship, she reviewed the scientific literature and found an oncology-specific acuity tool that was deemed valid and reliable. O’Leary then designed a study to investigate the acuity tool’s value for WCC7. Co-workers agreed to test the new assessment and they were able to chart trends in the health of patients, as well as how well the tool predicted fluctuations during a nurse’s assignment. O’Leary further broke down the data to find trends in the numbers of patients per nurse. As a result, she was able to create a graphic that visually demonstrated the sharp turns in patient sickness each day, from shift to shift, and throughout their hospital stay. “This is not only hard on patients but it’s hard on nurses,” O’Leary says. “Ultimately we wanted to show with real data how sickness impacts the patient, the whole unit, the flow of work, and how nursing assignments could be altered.” “I love research and finding my niche has been wonderful,” O’Leary adds. “We have a group here that really appreciates data, and if they know that our research will benefit patients, they’re all for it.” Next up: Luzunaris says the Wilmot Nursing Research Committee, a group comprised of nurses from various inpatient and outpatient locations, will evaluate ways to improve communication by using technology similar to a smart phone. Designed for the medical
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community, these types of devices stream vital signs, send alarms, and notify appropriate team members. They also have a text message-like feature while keeping information secure. Luzunaris believes the technology will simplify and speed up decision-making. “Sometimes all that’s needed is a quick ‘yes’ or ‘no,’ ” she says. But, as scientists, she and O’Leary know it’s important to first take a step back and investigate the effectiveness, costs, and efficiency of the communication devices. “We have a lot of nurses who question things here, and that’s good,” Luzunaris says.
Invasion of the “research nerds” Cancer research is often described as a “bench to bedside” process, starting in a controlled laboratory with fundamental science to understand the roots of the disease and ending, ideally, closer to the patient’s bedside with a new discovery about cancer or how a treatment might impact an entire population of patients. When nurses do research, their benches look a lot different. They work on the front lines, and they’re educated to see the whole person, from the biological to the spiritual side. Nurses bring a different perspective to the complex world of cancer research—one that focuses on patient experiences and quality of life. “My lens is different than that of a radiation oncologist or a molecular geneticist in a basic science lab,” says 13-year cancer survivor Kathy Rideout, Ed.D.
Chief Nursing Officer to Champion Research P.P.C.N.P.-BC, F.N.A.P., dean of the University of Rochester School of Nursing. “The scope of research has changed and it’s important that research is being done on every front. Being able to provide the tools to live with a chronic disease is just as important as a cure.” The possibilities are endless. Nurse scientists resolve urgent clinical problems such as preventing medication errors or infections; they investigate tools and systems to manage care; and they tackle behavioral issues related to cancer prevention, coping with getting sick, and living well beyond the diagnosis. In the end, nurse investigators have the same goals and objectives as other researchers: To supply valid and meaningful evidence to every decision made in an outpatient clinic or at the bedside. Wilmot nurses are formalizing their approach by launching a nursing research committee and encouraging collaboration across disciplines. As Rideout notes, a key distinction for an academic facility is that every member of the care team— from the physician, to the nurse, to the social worker—brings not only their individual expertise but “their own body of evidence to support decisions and a respect for team science. And when patients know what the latest evidence shows, it really resonates.” “The day of the lone researcher is really past us,” adds Jamie Oliva, Ph.D., A.N.P-C, B.M.T.C.N., a researcher, nurse practitioner, and teacher. “The questions today are so complex and the problems so numerous that all team members need a seat at the table.”
Rhonda Knapp-Clevenger, Ph.D., C.P.N.P., C.C.R.P., will join Wilmot Cancer Institute in December as its Chief Nursing Officer and as associate director, nursing, for Strong Memorial Hospital. For the past 20 years, Knapp-Clevenger has built her career in clinical nursing and research at the University of Colorado and its affiliate Children’s Hospital Colorado. She developed a formal scientist program and provided leadership and direction for nurse-initiated research. In her role as CNO, she will oversee Wilmot’s more than 300 nurses, including the regional operation, and will help expand the nursing research program. She will also hold a faculty appointment with the University of Rochester School of Nursing.
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COVER STORY
Marie Flannery, Ph.D., R.N., AOCN, and Jamie Oliva, Ph.D., ANP-C, BMTCN, study patient-reported outcomes and ways to improve care.
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Making things happen Marie Flannery, Ph.D., R.N., AOCN, has been part of Wilmot’s rich history of nursing research since the 1980s. She built on those early opportunities to advance her own studies and initiatives, and now as a nursing faculty member has the responsibility of training the next generation of nurse scientists. “By becoming a researcher, I could help more than one patient at a time,” says Flannery, who has presented her research nationally and internationally. Some of her past projects looked at ideal nurse ratios for patients who’re getting infused with chemo and better ways to identify troubling symptoms and side effects among cancer patients. She also discovered surprising patterns among the thousands of telephone calls that come into Wilmot from worried patients and families. The phone patterns revealed, for example, that lung and gastrointestinal cancer service lines received the most calls proportionately, and that pain complaints and test results were the chief reasons for the calls. Wilmot became more proactive as a result of her study and hired two additional nurses to manage the intake, Flannery says. The data was published in the Journal of Oncology Practice. Lately, her work is focusing on Wilmot’s Geriatric Oncology Program and finding ways to use electronics and the MyChart system to better connect patients with their caregivers. For example, in a National Cancer Instituteapproved study, Flannery’s team is studying whether electronic reporting is a reasonable way for cancer patients to tell of pain, depression, and other symptoms. Patients seen by four cancer center oncologists are being asked if they are willing to complete symptom surveys on MyChart and are being given iPads to take the surveys in clinic waiting rooms. Past research has established that patient reporting of symptoms results in improved outcomes. However, it is not clear how to make the process go smoothly, and thus the goal of the study is to establish whether the tool is feasible in a busy clinic.
Mary Jo Paciorek completes a symptom survey on a tablet as part of a study led by Marie Flannery, Ph.D., R.N., AOCN.
“We want to involve patients as much as possible, and by providing data in real time the health care team can intervene earlier,” she says. “It’s pretty powerful.” Oliva is also using modern technology to develop a separate study that would allow patients who’ve received treatment from Wilmot’s Samuel E. Durand Blood and Marrow Transplant (BMT) program to monitor their health at home and call in with concerns between scheduled oncology visits. Based on her specialized clinical practice in BMT, Oliva completed a doctoral thesis in 2016 that investigated graft-versushost disease, a transplant complication. Patients with leukemia or lymphoma who receive stem cells from an outside donor are more prone to graft-versus-host, where the donor’s immune cells attack the patient’s tissues and organs. Medications can control the disease but scientists do not fully understand the pathophysiology. Oliva investigated whether the number of T cells, a type of immune cell, in a patient’s blood sample was associated with graft-versus-host disease. In the next phase of her research, she’s exploring the use of a software program that would allow patients to keep track of their graft-versus-host symptoms on their own. As more nurses like Oliva seek advanced degrees, enrollment in research-focused doctoral programs has also climbed, according to the American Association of Colleges of Nursing. Teaching students to dig for evidence is a critical piece for translating science to clinical care. “Once the evidence is in,” Oliva says, “we can make things happen in the clinic.”
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COVER STORY
Karen Abbas, M.S., R.N. AOCN, and Tammy Clarke, M.S., R.N., OCN, BMTCN, focus their research on reducing patients’ risk of falling.
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Nurses as troubleshooters Knowing how to use data appropriately to benefit patients is the essence of an academic institution. Nurses play a crucial role in this effort because they’re tuned into clinical problems, big and small. A primary example is the nearly one million patients who fall and injure themselves each year in U.S. hospitals, making it one of the most common complications of patient care, according to The Joint Commission, the accrediting body for hospitals. Although it’s a widespread problem, Karen Abbas, M.S., R.N., AOCN, and Tammy Clarke, M.S., R.N., OCN, BMTCN, are determined to reduce the risk of falling at Wilmot with an evidence-based approach. They astutely recognize, however, that falling is not just a physical issue. “People with cancer can come into the hospital otherwise healthy, but treatment will weaken them and they don’t always realize it. And they want to maintain their independence,” Clarke says. Abbas agrees, adding: “Cancer patients express a loss of control. Their body has betrayed them and now they’ve lost the ability to simply walk around the room when they want to, and it’s very distressing.” Wilmot nurses had been using a tool provided by Strong Memorial Hospital, the main hospital on the University of Rochester Medical Center campus, to assess the fall risk of cancer patients as they arrived for admission to the cancer center. Classifying risk accurately can go a long way toward preventing falls, and they had concerns about the special needs and classifications for people with cancer, who are often older adults.
Abbas and Clarke discovered that the Cleveland Clinic developed a validated, fall-risk tool particularly for oncology, and launched a study to compare the standard tool to Cleveland’s tool. They’ve retrospectively reviewed 50 cases of people who fell and examined their initial risk assessment. It’s early in the investigation, but Abbas believes the eventual result will allow Wilmot’s team to design their own cancer-specific tool that suits the needs of this region’s unique population. “A more accurate assessment will help nurses do their jobs and patients better understand their limitations,” Abbas says. Two years ago, they took on a similar research project—this one involving small blood clots related to a certain type of central-line catheter for chemotherapy—and the results showed, to their surprise, that an older catheter produced fewer blood clots than a newer model among 75-100 leukemia patients. Like patient falls, peripheral-line blood clots are an issue that nurses, patients, and hospital systems grapple with across the country. Abbas was invited to share her study at a podium presentation at the Oncology Nursing Society 2016 annual meeting. “This is why we do research,” Abbas says: “To find something better for our patients and to make the practice of nursing more evidence-based.”
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How new science is helping surgeons remove tumors without disrupting a patient’s livelihood By Lydia Fernandez
Courtney L’Esperance remembers the day in March 2015 a neurologist told them that her husband Jonah had a brain tumor. “He said, ‘You have a tumor the size of a small apple.’ And I’m thinking it’s like one of those little kid crabapples.” Then they saw the MRI. It looked more like a baseball. “It was like someone punching me in the stomach,” Courtney recalls. They had been married only three weeks. They had just bought a house in Henrietta — a humongous fixer-upper. They were just 25, and a grade 2 astrocytoma was taking over the left side of Jonah’s brain. The tumor had to be removed, but getting to it could disrupt the areas of his brain that control speech, memory and dexterity — functions essential to Jonah’s work as a carpenter and his passion for playing guitar. Not removing it could mean that Jonah could lose the use of his tongue and his right arm and leg. With so much at stake, a local surgeon referred the couple to UR Medicine, where collaboration between cognitive scientists and neurosurgeons is bringing advances from the laboratory directly into the operating room to help patients with brain tumors. This team — featuring members of Wilmot Cancer Institute and the Del Monte Institute for Neuroscience — maps each patient’s brain in exquisite detail before, during and after surgery. They find a route to the tumor that will least disrupt critical functions, preserving the humanity and abilities of their patients.
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Jonah L’Esperance underwent extensive brain mapping as part of a research study before having surgery to remove a large tumor from the left side of his brain.
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Brad Mahon, Ph.D.
Web Pilcher, M.D., Ph.D.
Kevin A. Walter, M.D.
This work has immediate implications for individual patients, but the data it generates could also help those far into the future. Cognitive scientist Brad Mahon, Ph.D., and his team are aggregating the results of the pre- and post-operative tests to design a system that would allow neurosurgeons anywhere to plan their strategies better and to predict more accurately the impact of their operations. “We want to develop the next generation of algorithms, so that surgeons could eventually model surgery on the computer and then generate predictions about cognitive abilities,” Mahon explains. “They could test different surgical approaches and figure out if there is a difference if the incision is here or there.”
millimeters from person to person. If a tumor is present, then the variation can be even more significant. “The brain is highly plastic,” explains John Foxe, Ph.D., director of the Del Monte Neuroscience Institute. “If there’s a tumor or lesion, those functions will move as the tumor grows, so you can’t rely on the averages at all.” Before surgery, Mahon’s team pinpoints these functions using functional magnetic resonance imaging, or fMRI. With a magnetic field and radio waves, fMRI detects changes in oxygen concentration in the brain, highlighting areas engaged by different activities. Typically, when fMRI is used in surgery planning, the imaging is limited to about an hour. With Mahon, patients undergo an exhaustive battery of cognitive and behavioral tests over the course of nine hours. They also undergo diffuse tensor imaging, which maps the white matter that connects different parts of the brain. These images reveal in significantly greater detail what is likely to be affected by an operation. “With tumor surgery, we have to make an incision to remove the tumor, but to get margins around the tumor, you also have to remove small areas of functioning brain,” says Web Pilcher, M.D., Ph.D., who leads UR Medicine’s Neurosurgery department.
“What we want to do is not allow that to impact the human being that you have lying on the table.”
Not relying on the average As with other types of cancer surgery, the goal of brain tumor resection is to remove as much of the tumor as possible. The challenge is that the brain is a complex network of billions of brain cells, and any incision can sever important connections in that network, potentially leaving patients without essential abilities. While the average brain is organized in roughly the same way, the control centers for different functions can vary by crucial
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Mapping, testing, verifying For Jonah L’Esperance, that included preserving his ability to speak, walk, and use tools to craft furniture and remodel kitchens. In the three weeks before his surgery, Jonah met Mahon and learned of the opportunity to participate in the study. He decided to go forward with the tests. In the fMRI, Jonah lay on his back and looked at a mirror placed above him at a 45-degree angle, reflecting images from a computer screen. “I would watch a slide show in there and I would have to think about everything I’m seeing,” Jonah says. He had to repeat sentences and melodies, read words and do basic math. “There were other tests where I would have to — with my hand at my side — act out using tools, like pretending to use a hammer, screwdriver, scissors, stuff like that,” Jonah says. “Then someone else would come in and tap my toes or my fingers, and I would just concentrate on where they were tapping to light up that part of the brain. It was cool.”
Diffuse tensor imaging: Using this new technique, cognitive scientist Brad Mahon, Ph.D., mapped the nerve fiber pathways in Jonah’s brain. The pathways important for language, shown here in orange, run through the tumor, reconstructed in black, on the left side of his brain.
He completed other tests outside the fMRI on a computer and on paper. From all of this came a picture of exactly where Jonah’s tumor had grown among the parts of his brain that control sensory and motor function and his ability to use tools and understand threedimensional space. It also showed the tumor enveloping a crucial neural fiber pathway connecting his speech comprehension and speech production centers. This picture helped Pilcher come up with a plan to remove the tumor with the least disruption to Jonah’s abilities. But the surgery would be complicated, and severing that neural pathway would be unavoidable. Jonah’s team expected he would come out of the operation with conduction aphasia, a condition that could cause Jonah to have trouble repeating phrases and finding words.
fMRI map: This functional MRI map of Jonah’s brain precisely locates the regions that support language (green), primary control of the right hand (red), skilled use of the right hand (yellow), and number knowledge and numerical competency (purple). His surgeon used these maps to find the best way to remove the tumor with the least possible disruption to Jonah’s abilities.
In the operating room, Pilcher opened Jonah’s cranium, and live images of his brain were projected on a large screen. The video of his brain was overlaid with the fMRI results using a system developed by Mahon and his team. Before making an incision in the brain, Pilcher needed to verify the location of Jonah’s language skills and find the best way in. To do this, though, Jonah needed to be awake, and anesthesiologist Jeffrey Kolano, M.D., brought him out of sedation. Lying on his side, looking at the screen of a tablet, Jonah began naming the images he’d see. At the same time, Pilcher used a probe to stimulate different places on his brain, looking for the best entry to remove the tumor. “There would be drawings of stuff and I’d have to say what it was,” Jonah says. “I’d have to say, ‘This is an umbrella,’ ‘This is a sailboat.’ That way if the sentence
started getting weird, they would stay away from that part of the brain.” Pilcher marked each location he stimulated with a number to help identify an area safe for him to make an incision. Each of those spots was assigned coordinates that corresponded to the pre-op fMRI for the scientists to study later. Jonah remained awake as Pilcher made the incision and began removing the tumor. He continued to do tests and talk with the OR team, who also helped him FaceTime with Courtney and his family — a crew of more than 30 crammed in the waiting room. Jonah was groggy from the sedation, but also thirsty. “At one point, they were like, ‘How are you doing?’ and I was like, ‘I want coffee,’” he recalls, laughing.
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“We want to develop the next generation of algorithms, so that surgeons could eventually model surgery on the computer and then generate predictions about cognitive abilities.”
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Life after surgery About 40 to 50 patients a year at UR Medicine undergo this kind of extensive brain mapping and awake surgery as part of this collaborative research study, which is funded by the National Institutes of Health. While many of these patients have brain tumors, this procedure is also used with patients who have epilepsy, venous malformations called cavernomas, and other conditions that require surgery in parts of the brain that control critical functions. “This gives us more feedback and allows us to be more aggressive,” says Wilmot neurosurgeon Kevin A. Walter, M.D. “It also allows us to work on better rehab. The earlier you can identify the problem, the better the results.” Jonah underwent weeks of rehabilitation with speech, physical and occupational therapy every day for hours. He couldn’t hold a spoon. He was nervous to try playing his guitar and shy about singing. He struggled to say words that he recognized on paper and the names of the people who came to visit. “One of the days, every time I’d try to say something, all I could say was ‘Tony Pepperoni,’” Jonah says, the name of the pizza shop where he’s worked since high school. “I knew I was saying it wrong, but I couldn’t get anything out.” He learned tricks to help him along — like trying to sing or imagine the words so that another part of his brain would engage and bring it out. Family and friends would quiz him, too. “Courtney’s dad would hold up an acorn and be like, ‘What’s this?’ He’d point to an airplane and he’s like, ‘What’s that?’” Jonah says. About two months after his surgery, with his head healing and his words
returning, Jonah went back to see Mahon and his team to repeat the cognitive tests. He also underwent six weeks of low-dose chemotherapy and radiation, followed by more chemo. Several months later, he returned Mahon’s lab for another round of cognitive testing. Each time, his abilities improved, and Mahon could see that Jonah’s brain was remapping itself to compensate for the tissue that had been removed during surgery. The connection between his language comprehension and language production centers was changing, and, Mahon suspects, rerouting to the right hemisphere of his brain. Jonah, who had gone into the operation just wanting to be the same as before, was playing his guitar again and back to crafting coffee tables and countertops. “I still remembered how to use all the tools,” Jonah says. “It was like riding a bike.”
Space to innovate For Mahon and his team, watching Jonah’s progress prompted a series of new hypotheses to explore with future patients. They began to wonder whether there is something unique about the brains of patients like Jonah that allows them to recover from conduction aphasia that isn’t present in patients who don’t recover. If so, they wondered, would it be possible to encourage that feature among patients who may be less likely to recover? Each case reveals new details about the brain’s structure, functions and resilience — adding to the understanding of how the brain works. And with every case come new questions: When functional centers are activated, why do less critical regions light up on the fMRI too? How does interrupting
Jonah and Courtney L’Esperance kayak on the Erie Canal. They bought the kayaks shortly before Jonah learned he had a brain tumor that could have cost him the use of his right arm and leg.
white matter pathways affect brain function? How can the information about the way the brain re-maps itself as tumors grow and are removed be applied to other situations such as stroke? “We want to develop a better tool to winnow the future fMRI maps to make better predictions about what’s going to be affected,” Mahon says. “We want to improve the quality of the fMRI data and the quality of analysis and interpretation of data.” Although technology in the field of brain and cognitive science has advanced rapidly over the past two decades, its translation into health care has been slower.
“fMRI still only has a marginal role in neurosurgery, even though it’s been around for about 20 years,” Mahon says. “There’s space to innovate here.” His collaboration with the Neurosurgery team is making that possible. “Translational research is the last step in taking a scientific discovery into clinical practice,” Walter says. “It’s a process like this, building on what we know.” For families like Jonah and Courtney, it’s also an opportunity to make a difference. “I immediately thought, let’s do it because it’s only going to benefit you and other people who have tumors,” Courtney remembers.
Since then, they’ve finished the renovations on their fixer-upper and are looking for a new home with more space for Jonah’s workshop. “As with any part in life, you just need patience,” Jonah says, thinking back on his experience and what it has meant. “I was glad to help with that. It was cool.”
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Community Focus Events held by groups and individuals in the community are vital to Wilmot’s success. They provide necessary funding for research and patient care. To learn more about third-party events or how to host your own, contact Tiffany Paine-Cirrincione at tiffany. paine@rochester.edu or (585) 276-4715. We are excited to share that in total for the 2016-17 fiscal year (July 1 through June 30), our third-party community groups have raised nearly $500,000. Additionally, at the 2017 Wilmot Warrior Walk, our community raised $170,000. We’d like to thank all those who helped make this possible, including the following groups: 4 Performance – American Junior Golf Classic Adding Candles for a Cure Atria Greece Barbara Occhipinti/Fico Memorial Cancer Fundraiser Blue September Blow the Whistle on Cancer Breathe Yoga Brighton High School Field Hockey Byron-Bergen Girls Soccer Team Coop Cup Cornell’s Jewelers Watch Program Cupcakes for Cancer Diane Fuest and Friends Dudley Elementary School (Fairport) Edelman Gardner Cancer Research Foundation Fairport Educators Association Fairport Football Booster Club Flaherty’s Three Flags Inn For Pete’s Sake Golf Tournament Geneseo Central Schools Take Back the Night Golden Soccer Challenge Goldwell Symposium Highlands at Pittsford KM Memorial Golf Tournament Kids Café/Flew the Coot Theater Kovalsky Carr Electric Supply Linda Clifford Memorial Jamboree Meaghan’s Run 5K Race/Walk Michael Contestabile Memorial Golf Tournament Mo Open Golf Tournament Nancy Golden Gulino Fundraiser Nazareth Women’s Soccer Team Oswego Men’s Lacrosse Team Order of the Sons of Italy NYS Lodge Foundation Palmer/Head-Strong Golf Tournament Pancreatic Cancer Association of WNY Penfield High School Boys Soccer Team Ray Dutcher Jr. Memorial Golf Tournament Retired Professional Firefighters Against Cancer Rochester Academy Charter School Sackett Jeffords Memorial Golf Tournament Scare Brain Cancer Away 5K Stand Against Cancer Steel Lillies 5K Walk Steve’s 5K to Run Down Cancer Steve Coleman Memorial Golf Tournament Strollin’ for the Colon Towpath Bike Community Foundation Us TOO 22 find us on Facebook and Twitter
At the Crossroads of Philanthropy and Science
The Cadregari Family To her family, Georgette Marie Cadregari was a mentor, a confidante, and Renaissance woman. She laid tile, painted portraits, managed the family finances, raised three children, adored her grandchildren and deeply loved the man she married more than 60 years ago. “She was the wind beneath our wings,” her husband Carl Cadregari says. “She took care of all of us.” In her memory, the Cadregari family created an endowment fund to support lymphoma research at Wilmot Cancer Institute. Georgette was diagnosed with lymphoplasmacytic lymphoma (LPL), a rare blood cancer, in 2009, and she continued to be her family’s source of strength until she died in 2015 of other causes. “We wanted to honor her memory and find some way to aid someone else,” Cadregari says. “We wanted to continue to enhance research and the ability of teams of investigators to make strides in care,” says son Carl G. Cadregari. The endowment supports the maintenance of a database that Wilmot’s lymphoma program uses to collect and analyze data on patients who have been seen at least once by the team. The database is linked to the program’s tissue bank, which allows researchers to look back at samples from biopsies, and it also allows Wilmot to collaborate with other institutions on national-scale clinical trials and other studies. “This is an incredibly important tool,” says Clive Zent, M.D., who leads the lymphoma program. “It lets us know with real granularity the experiences of our patients. It allows us to quantify the problems of patients so we can look for solutions.” For example, the database was central to a collaboration with eight other medical centers to determine the best order and timing of three relatively new drugs for patients with chronic lymphocytic leukemia (CLL). It was key to another study that
analyzed how the availability of novel therapies has changed the risk of infection among CLL patients. Wilmot pharmacists Margaret Helber, Ph.D., PharmD, and Jeremiah Moore, PharmD, BCOP, also used the database in collaboration with Zent to study the use of a targeted therapy called ibrutinib in patients with LPL, also known as Waldenstrom macroglobulinemia, the same rare cancer that Georgette Cadregari had. Their work will help pharmacists across the country who may have little or no experience with the use of this drug in the management of LPL patients. “A database like this is not the sort of resource usually funded by the National Institutes of Health or other large funders, but it’s absolutely critical to the conduct of research,” Zent says. “We are incredibly grateful for the support from the Cadregari endowment.” For the Cadregari children, the endowment is also a way to recognize the care that their parents have received at Wilmot and to honor their parents’ love story. “What Wilmot has done for my family,” says daughter Laura Cadregari, “they’ve supported them like no other organization I’ve seen.” Their parents started dating as teenagers and married after Carl finished graduate school. His job as an expert in plant genetics took them around the country and the world. Through all their moves and travels, Georgette was unconditionally supportive. “She loved my dad from the top of his head to the tips of his toes,” Carl G. Cadregari says. Georgette also inspired her children. Son David says that her service to those in need led him to follow in her footsteps. Whether it was working with the Seaton Sisters group at St. Mary’s Hospital or as a post-adjudication review board volunteer, the gift in her name well represents her attitude of service to the community, the family says.
Their gift is a way for them to honor a woman who shared her amazing talents, incredible humor and a big heart. “It keeps her memory alive,” Laura Cadregari says.
Georgette Marie Cadregari
Research assistants Annalynn Williams and Philip Meacham discuss Wilmot’s lymphoma database with patient John Archibald. The database is an essential tool for the lymphoma program.
About this feature Every donor and community organization has their own reason to give to cancer research. In this space in Dialogue, we’ll share what motivates Wilmot Cancer Institute supporters.
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NEWS BRIEFS
Wilmot among First to Offer Landmark Immunotherapy The U.S. Food and Drug Administration recently approved a promising new type of immunotherapy— known as CAR T-cell therapy—to treat adults with aggressive lymphoma. And Wilmot Cancer Institute is expected to be the only center in upstate New York between Michigan and Boston to offer it. The therapy is one of the most powerful to emerge in recent years. Originally developed by the National Cancer Institute, CAR T-cell treatments have since been advanced by several biotech firms, including Kite Pharma in California. Its drug, called Yescarta, was tested in clinical trials in top lymphoma programs across the country, including Wilmot’s. The treatment works by boosting a patient’s own immune system to seek and kill the cancer cells involved in diffuse large B-cell lymphoma, a common type of blood malignancy for which there is no cure.
Scientists take a patient’s extracted T-cells, the infection fighters in the immune system, and reprogram them. When the cells are infused back into the patient, they’re trained to attack a protein that sits on the surface of lymphoma cells. More than 100 people took part in a nationwide study of Yescarta in 2015-2016: 80 percent of patients responded in some way and 50 percent had their tumors disappear. Three patients died. All of the study participants had exhausted other standard treatments and only had a few weeks or months to live without the experimental therapy. “The statistics are out of the ballpark considering the health of the patients, and we’re excited about the potential of this therapy,” says Patrick M. Reagan, M.D., who will run Wilmot’s clinic, certified by Kite to deliver Yescarta. “But we’re also mindful that it’s very new and that patient safety is our primary objective. We plan to roll it out slowly and carefully.” Risks and serious side effects accompany CAR T-cell therapy, and Wilmot has specially trained teams to minimize risks and manage side effects when they occur.
Study to Investigate Muscle Loss among Children with Cancer A University of Rochester Medical Center researcher received $1.7 million to study and potentially treat the muscle loss that often plagues childhood cancer survivors as they age. The five-year grant to Joe V. Chakkalakal, Ph.D., assistant professor of Orthopaedics, is a result of a collaboration and seed funding from the Wilmot Cancer Institute, which allowed him to generate the data to obtain the larger grant from the National Cancer Institute. Chakkalakal studies muscle stem cells in connection with skeletal muscle decline. Young cancer patients who undergo radiation therapy sometimes experience sarcopenia, the accelerated loss of lean body muscle tissue and strength. Sarcopenia-related muscle atrophy is associated with muscle stem cell loss and chronic, low-grade inflammation. The new investigation will try to determine if childhood radiation treatments destroy muscle stem cells and thereby impair the young musculoskeletal system as it tries to mature properly. In addition, Chakkalakal is studying the factors that accelerate sarcopenia and how to prevent the systematic loss of muscle stem cells and skeletal decline caused by radiation. Although the overall five-year survival rate for children who
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have cancer is nearly 80 percent, it’s important to alleviate the long-term consequences from cancer treatment in young people, Chakkalakal says. For example, the majority of childhood survivors who receive radiation therapy begin to experience limitations in strength and mobility by age 40 that are more commonly linked to older adults, he says. The physical limitations can eventually lead to falls, fractures, and other muscle weaknesses. Eddie Schwarz, Ph.D., the Burton Professor of Orthopaedics and Rehabilitation and director of URMC’s Center for Musculoskeletal Research, and Jacky Williams, Ph.D., professor of Environmental Medicine and Radiation Oncology, are collaborating with Chakkalakal on this project. All are members of the Wilmot research team.
Noel Appointed to Lead Hem/Onc Ambulatory Operations Assistant professor Marcus Noel, M.D., has been named Director of Ambulatory Operations for UR Medicine’s Division of Hematology/Oncology. Noel will serve as the senior clinical administrative faculty leader overseeing clinical care and clinical operations for medical oncology ambulatory services, including Wilmot Cancer Institute’s outpatient clinics and infusion centers. Noel will work closely with nursing and Wilmot leadership in fulfilling these responsibilities. “Dr. Noel is a natural leader and will do a fantastic job balancing the complexities and requirements of cancer care and clinical research with patients’ and families’ needs for convenience, expedience, familiarity, and warmth” says Aram Hezel, M.D., chief of Hematology/Oncology. Noel graduated from the Robert Wood Johnson Medical School at the University of Medicine and Dentistry of New Jersey. He completed his internal medicine residency and oncology fellowship training at the University of Rochester Medical Center prior to joining the Division of Hematology/Oncology. He became an assistant professor in 2015. His expertise is in gastrointestinal oncology and clinical research focuses on development of novel therapies for these diseases, and he leads the GI oncology clinical research team.
Scientists Identify New Way to Slow Cancer Cell Growth Cancer is an extremely complex disease, but its definition is quite simple: the abnormal and uncontrollable growth of cells. Researchers from the University of Rochester’s Center for RNA Biology have identified a new way to potentially slow the fast-growing cells that characterize all types of cancer. The findings, reported recently in the journal Science and funded by the National Institutes of Health, were made in kidney and cervical cancer cells in the laboratory. Although they are a long way from being applied in people, they could be the basis of a treatment option in the future, the authors say. All cells go through a series of events that culminate in orderly cell growth and division, a process called the cell cycle. In cancer, the cell cycle is out of whack, and cells divide without stopping and invade surrounding tissues. Researchers identified a protein called Tudor-SN that is important in the preparatory phase of the cell cycle — the period when the cell gets ready to divide. When scientists eliminated this protein from cells, using the gene editing technology CRISPR-Cas9, cells took longer to gear up for division. The loss of Tudor-SN slowed the cell cycle. “We know that Tudor-SN is more abundant in cancer cells than healthy cells, and our study suggests that targeting this protein could inhibit fast-growing cancer cells,” says Reyad A. Elbarbary, Ph.D., lead study author and research assistant
professor in the Center for RNA Biology and the department of Biochemistry and Biophysics at the University of Rochester School of Medicine and Dentistry. Elbarbary, who works in the laboratory of senior study author Lynne E. Maquat, Ph.D., a world-renowned expert in RNA biology, adds that there are existing compounds that block Tudor-SN that could be good candidates for a possible therapy. Maquat’s team discovered that Tudor-SN influences the cell cycle by controlling microRNAs, molecules that fine-tune the expression of thousands of human genes. When Tudor-SN is removed from human cells, the levels of dozens of microRNAs go up. Boosting the presence of microRNAs puts the brakes on genes that encourage cell growth. With these genes in the “off” position, the cell moves more slowly from the preparatory phase to the cell division phase. “Because cancer cells have a faulty cell cycle, pursuing factors involved in the cell cycle is a promising avenue for cancer treatment,” says Maquat, director of the Center for RNA Biology and the J. Lowell Orbison Endowed Chair and professor of Biochemistry and Biophysics. Maquat, who also holds an appointment in the Wilmot Cancer Institute, and Elbarbary have filed a patent application for methods targeting Tudor-SN for the treatment and prevention of cancer. Research next steps include understanding how Tudor-SN works in concert with other molecules and proteins so that scientists can identify the most appropriate drugs to target it. Keita Miyoshi, Ph.D., staff scientist in Maquat’s lab, served as lead study author with Elbarbary. Jason R. Myers and John M. Ashton, Ph.D., from the UR Genomics Research Center played an instrumental role in the study analysis.
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Marshall Lichtman to receive Lifetime Achievement Award from ASH Marshall A. Lichtman, M.D., a hematologist/oncologist and former dean of the University of Rochester School of Medicine and Dentistry, will receive one of the highest honors in his field from the American Society of Hematology (ASH) for an exceptional, 51-year career and many lasting contributions toward understanding blood cell diseases. ASH will present the Wallace H. Coulter Award for Lifetime Achievement in Hematology to Lichtman at the society’s annual meeting in December. “I’m deeply honored,” says Dr. Lichtman created an Lichtman, 83, professor emeritus alphabet from abnormally in the Department of Medicine, shaped red blood cells. He Hematology/Oncology, and of used letters from his alphabet Biochemistry and Biophysics. to reproduce a favorite quote. “The American Society of Hematology membership includes a lot of people of achievement and I feel fortunate they chose to recognize me this year.” Lichtman built a career in Rochester as a physician, researcher, educator, administrator and mentor after joining the University in 1960 for post-doctoral training and residency. He was the senior associate dean for academic affairs and research for 10 years and subsequently, the sixth dean of the medical school, serving from January of 1990 through December of 1995.
“Marshall Lichtman spent his entire distinguished career in Rochester and he continues to have a strong mentoring role for our leukemia team. It is a tribute for Wilmot that he is being recognized by ASH in this way,” says Jonathan W. Friedberg, M.D., M.M.Sc., director of the Wilmot Cancer Institute and also a blood cancer specialist. Lichtman studied leukemia cell membranes. He was motivated by a phenomenon known as contact inhibition. In cell biology, this is when a layer of dividing cells collides; under normal circumstances they somehow recognize this surface contact and stop replicating. But when cells are cancerous they lose contact inhibition and continue to divide uncontrollably, growing over each other despite cell-to-cell contact. Lichtman thought this phenomenon important and made several important scientific observations about leukemic cells and how they differed from normal cells. He also developed a simple blood test for measuring hemoglobin/oxygen affinity — a test that continues to be used by hematologists in the lab. This test came out of a project with the U.S. Army, which was concerned about troops succumbing to altitude sickness. Lichtman was studying ways to improve red blood cell function and delivery of oxygen to the body, which proved useful in several diseases. Lichtman became chief of the URMC Hematology Unit in 1975, specializing in leukemia. He was frequently consulted for help in diagnosing and managing many of the most complex hematologic diseases. He’s written several textbooks, and notably he co-edited Williams Hematology for seven editions and wrote numerous chapters on blood cell diseases. He was also instrumental in starting the Samuel E. Durand Blood and Marrow Transplant program at Wilmot Cancer Institute in 1989.
Urology Researcher Lands among PLOS ONE’s Top Cited Papers A bladder cancer study led by Carla Beckham, M.D., Ph.D., is among the top 25 percent most-cited papers published by the journal PLOS ONE in 2016. Beckham, an assistant professor of Urology at the University of Rochester Medical Center and the Wilmot Cancer Institute, treats patients for bladder cancer and other urological diseases, and conducts research in RNA biology. Her study suggested that a type of RNA molecule may potentially serve as a biomarker for bladder cancer as part of a panel of molecules. PLOS ONE notified Beckham that her paper has been viewed more than 6,000 times, and 38 percent of the views resulted in downloads of the article. Beckham’s lab investigates long non-coding RNA (IncRNA), a diverse class of RNA molecules. Researchers showed that a particular IncRNA known as HOTAIR is enriched in the urinary
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exosomes of patients with high-grade, muscle-invading bladder cancer. The paper also suggested that HOTAIR could be a promising target for treatment, as scientists were able to show that by knocking out the expression of the HOTAIR gene in bladder cancer cells in the lab, they could reduce the cancer cell’s invasive traits. HOTAIR has been previously shown to play a significant role in tumor initiation and progression in many cancers, particularly breast cancer. Her research not only raised the importance of HOTAIR in bladder cancer, but the lab also used RNA sequencing to identify four additional IncRNAs in the urinary exosomes of patients with that disease. Further investigation is required, however, as scientists move forward to develop RNA-based therapies. Beckham is funded by the Wilmot Cancer Research Fellowship Program and the URMC Clinical & Translational Science Institute.
Radiation Oncology Offers Metastatic Cancer, Palliative Care Service The Department of Radiation Oncology at Wilmot Cancer Institute now offers a Metastatic Cancer and Palliative Radiation Therapy service to help patients manage pain and other cancer-related symptoms. The service makes it easier for patients who do not already have a relationship with Radiation Oncology to connect with the team. In non-urgent situations, these patients can be referred directly by their oncology team, improving communication among the physicians and satisfaction among the patients and their families. For more than a third of radiation oncology patients, the goal of radiation therapy is management of pain and symptoms. This new service, led by Haoming (Carl) Qiu, M.D., assistant professor of Clinical Radiation Oncology, works closely with the team from Palliative Care. “We have cultivated a rich working relationship with our Radiation Oncology colleagues,” says Robert Horowitz, M.D., Chief of Palliative Care at UR Medicine. “It’s one of the very few such formal collaborations in the nation.”
Wilmot to Lead Study of Vitamin D in Lymphoma Wilmot Cancer Institute will lead one of the first national trials to evaluate whether adding vitamin D to standard therapy for lymphoma will help patients. With $3 million in National Cancer Institute funding, principal investigator Jonathan W. Friedberg, M.D., M.M. Sc., Wilmot’s director, will oversee the research in Rochester and at several other leading cancer centers including the Mayo Clinic, Emory University, Weill Cornell Medicine, Washington University, and MD Anderson. Patients with follicular lymphoma (FL) and other low-grade lymphomas will be eligible for the five-year study. FL is the second most common and the most prevalent of the nonHodgkin lymphomas in the U.S. Although it is generally incurable, in recent years newer therapies have resulted in FL being treated like a chronic disease, boosting the median survival to about 20 years. The randomized, phase 3, blinded study will enroll approximately 200 patients. Researchers will compare the outcomes of people who receive standard rituximab therapy alone (plus a placebo pill) to a combination of rituximab and 2000 I.U. oral vitamin D daily for three years. They also will conduct genomic tests on tissue samples to determine subsets of patients who might particularly benefit from vitamin D therapy. Friedberg noted that some FL patients die earlier than expected, and many others require intermittent treatment for the rest of their lives that can be toxic and expensive, potentially exceeding $100,000 per patient a year. “If vitamin D can boost the effectiveness of rituximab early in the disease process,” Friedberg says, “it could result in an immediately available, inexpensive and well-tolerated new standard treatment approach.”
In a prior study published in 2015, Friedberg discovered that when an individual has lower vitamin D levels at the time of the follicular lymphoma diagnosis, it strongly correlates with an earlier death. Vitamin D has received a lot of attention in recent years. People get varying amounts of vitamin D naturally from sun exposure, and from fatty fish and fortified foods such as milk and orange juice. In 2010 the nation’s top scientific advisory panel, the Institute of Medicine, recommended that most children and adults also consider taking daily dietary supplements of 600 international units. In the context of cancer, prior studies by the University of Rochester Medical Center and others have linked low vitamin D levels with a worse prognosis of breast and colon cancer, and have shown health disparities in people with darker skin who produce less vitamin D in response to sun exposure. However, it is not known exactly how vitamin D modifies or contributes to cancer risk.
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Research Links Four Genes to Pancreatic Cancer Survival Wilmot investigators took part in a large study showing that alterations in four main genes are responsible for how long patients survive with pancreatic cancer. Published in the journal JAMA Oncology, the study is important because until now the presence and patterns between the genes and disease progression was not clearly established. After the tumors of 356 patients were surgically removed, researchers extracted DNA from the cancerous tissue and conducted next-generation DNA sequencing on the specimens. The analysis centered on the activity of the KRAS, CDKN2A, SMAD4, and TP53 genes. Results showed that patients who had three or four of the altered genes had worse disease-free survival (the time between surgery and when the cancer returns), and overall survival (from surgery to death), compared to patients with one or two altered genes.
“The research helps us to understand how the molecular features of pancreatic cancer impact prognosis on an individual level and gives us more facts to guide patients, and importantly, to design future research studies,” says study co-author Aram Hezel, M.D., chief of the Division of Hematology/Oncology at Wilmot. Pancreatic cancer is aggressive and generally has poor survival odds. Patients who can undergo surgery as part of treatment often live longer and some patients fare best when they can receive chemotherapy prior to surgery. But having customized, molecular information will provide an even greater understanding of how the disease is likely to progress in each patient, Hezel says. Wilmot collaborated with Dana Farber/Brigham and Women’s Cancer Center in Boston and the Stanford Cancer Institute. David Linehan, M.D., a pancreatic cancer expert and director of clinical operations at Wilmot, also was part of the investigative team along with Wilmot oncologist Richard Dunne, M.D., and pathologist Jennifer Findeis-Hosey, M.D.
What’s in Your Gut? Bacteria Might Impact Response to Cancer Therapy Among 112 individuals with melanoma, those patients who had a more diverse gut microbiome, filled with plenty of “good” bacteria, did better and saw their tumors stabilize while taking a six-month course of a type of immunotherapy called anti-PD1 treatment. (Anti-PD1 drugs became more widely known after former President Jimmy Carter began using them to control his metastatic skin cancer. The drug works by boosting the body’s natural immune fighters against cancer cells.) Published in the journal Science, the study results are exciting because researchers were able to correlate, to a specific micro-
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biota, the immune system’s ability to combat cancer, says study coauthor Peter Prieto, M.D. M.P.H., assistant professor of Surgery at the University of Rochester Medical Center and Wilmot Cancer Institute. The research will likely lead to new strategies, such as testing potential probiotics in clinical trials to boost the response of standard treatments for melanoma, he says. Prieto took part in the investigative project while at the MD Anderson Cancer Center in Texas before he joined the faculty at URMC, where he’s continuing to study the microbiome. The ultimate goal, Prieto says, is to identify a “microbiome signature,” like a living biomarker in the form of healthy bacteria. In the meantime, consumers, cancer patients, and the medical community should be concerned about the overuse of antibiotics, which contributes to unhealthy gut flora and limits immune function, he says.
SAVE THE DATES Survivorship Symposium Spring 2018 Join Wilmot’s Judy DiMarzo Cancer Survivorship Program for a daylong symposium to address issues faced by cancer survivors, including family and work issues, lifestyle changes and more. Resource and referral information will also be available for survivors and caregivers. Watch for details, including registration, at wilmot.urmc.edu/events.
Survivors Night at the Ballpark Friday, Aug. 10, 2018 Celebrate life beyond cancer during Wilmot Cancer Institute’s Survivors Night at Frontier Field in Rochester. All cancer patients, survivors and caregivers are invited to attend at a reduced rate. The game starts at 7:05 p.m. Watch for details, including ticket information, at wilmot.urmc.edu/events.
Wilmot Warrior Walk Sunday, Sept. 9, 2018 Join us in celebrating all cancer survivors, remembering those we’ve lost and supporting local cancer research. The event features a 5K, 10K and 1-mile walk, as well as a post-race celebration. Funds support cancer research and Wilmot’s Judy DiMarzo Cancer Survivorship Program. Check for details, including registration and sponsorships, at WarriorWalk.urmc.edu.
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