Wilmot Cancer Center at Forefront of Survivorship Research

Wilmot Cancer Center at Forefront of Survivorship Research

Does the clock on survivorship start at diagnosis or five years later? Debate and various definitions among oncologists might be confusing, but one thing is crystal clear: Today, millions of cancer survivors are alive at all points in time, bringing a need for greater understanding of how to live well after cancer.

The Wilmot Cancer Center has a rich and deep history in research related to challenges faced by cancer survivors. For decades, Wilmot scientists have been studying the risks of second cancers, sleep disorders, nausea, and post-treatment decline of cognitive function. The notion of accepting responsibility for helping people cope with the physical and psychological effects of treatment, and improve quality of life, not just length of life, is part of the Wilmot Cancer Center tradition. The University of Rochesters long association with Philip Rubin, a pioneer in cancer radiation biology and cancer survivorship research, put Wilmot at the forefront and outstanding research leaders such as Gary Morrow, Ph.D., Lois Travis, M.D., Sc.D., and Jacqueline Williams, ,Ph.D., are pushing a new, modern agenda.

Just as treatment is evolving, so are thoughts and ideas about survivorship. Instead of simply identifying and characterizing common and sometimes debilitating side effects of treatment, scientists are now looking for specific ways to lessen the side effects of chemo, radiation, and targeted therapy, and calculating who benefits the most and why.

They have already learned, for example, that fatigue and brain fogginess associated with cancer is very different from what most people feel when they skip a few good nights of sleep. And that exercise, once frowned upon out of concern that it was too taxing, might actually make some cancer patients feel better and perhaps do better.

In the future, risk estimates and prediction models will become the norm. Researchers and physicians will know why some people feel very sick during and after chemotherapy and others not as much. They will continue to design effective interventions, and standardize them for many different situations. Emerging data will go a long way toward establishing research priorities, personalizing treatment, and using resources smarter, as the number of survivors is expected to reach 18 million people by 2020.

After all, survivorship research is really about how to thrive, not just survive.

CCOP Research Program a National Leader

Over the span of a 36-year career, Gary Morrow, Ph.D., has made landmark contributions to research related to cancer survivorship and symptom management. As the head of Community Clinical Oncology Program (CCOP) at the Wilmot Cancer Center, Morrow has helped position the University of Rochester Medical Center and its multidisciplinary team of investigators at the forefront of cancer control research.

The CCOP program at URMC is part of a national network of clinical research programs that develops, conducts, monitors, and evaluates clinical trials and trains researchers. Established in 1983, it was the first CCOP funded in a cancer center in the U.S.

Morrows group includes a bevy of talented researchers who have contributed groundbreaking studies that have had national recognition and impact. Following is just a sampling of the recent studies conducted by CCOP researchers:

The Positive Effects of Exercise

Exercise generally helps the nations 12 million cancer survivors, and Karen Mustian, Ph.D., M.P.H. and her team are working toward being able to prove, with scientific certainty, that prescriptions for daily yoga or 20 minutes of walking will likely extend a patients survival.

In 15 years we've gone from being afraid to recommend exercise to people with cancer, to having enough data that shows, by and large, it is safe and effective, particularly for relief of treatment side effects, said Mustian, assistant professor of Radiation Oncology at URMC and an exercise psychologist specializing in cancer. But when a patient walks in the door, he or she wants to know how to tailor exercise to their own situation. Should I bike, walk, or lift weights? Is there anything I should avoid? Can certain exercises lower my fatigue? And the scientific community has not settled into a place where we've developed explicit exercise prescriptions, or can effectively narrow the choices for patients.

Several URMC studies suggest that knowing how to develop and apply specific exercise programs (dose and timing to achieve a certain outcome) is a realistic goal.

Mustian and Lisa K. Sprod, Ph.D, investigated physical activity among older people, a group they describe as often overlooked and underestimated in terms of their ability to live with cancer. Just last June, she and Mustian presented findings from two of their studies at the annual meeting of the American Society of Clinical Oncology (ASCO), in a session titled, Staying Bold While Old.

In another exercise-related study, Luke J. Peppone, Ph.D., a research assistant professor, investigated the effects of a yoga program on women with breast cancer who were taking aromatase inhibitors, medications that deplete estrogen and often cause severe menopause-like symptoms. A frequent complaint is joint pain and muscle aches, sometimes making it difficult for women to get out of bed or grip a fork and knife.

Peppone said a high percentage of breast cancer survivors discontinue aromatase inhibitor therapy because of side effects, putting them at greater risk for cancer recurrence. His study measured the self-reported quality of life and physical discomfort among 95 women taking aromatase inhibitors and 72 women who were not taking the drug. Each group took part in a four-week gentle yoga program. The women taking aromatase inhibitors reported a significant reduction in pain, muscle aches, and total physical discomfort, Peppone said. The study will serve as a pilot to launch a larger study of exercise to relieve musculoskeletal pain.

In a controlled study of yoga therapy in middle-aged, mostly female cancer survivors showed that a four-week, customized gentle yoga plan significantly reduced perceived difficulty with memory. Michelle C. Janelsins, Ph.D., research assistant professor at Wilmot, randomized patients to one of two groups: standard follow-up care after receiving adjuvant cancer treatment, and standard care plus a program that consisted of breathing exercises, gentle Hatha and restorative yoga postures, and meditation. The yoga group had significantly reduced memory difficulty compared to the standard care control group.

Controlling Nausea

Nausea is a difficult condition to study, even though it is among the most common reported side effects of cancer medications. Since 1996 the CCOP group has investigated many aspects of nausea and contributed several significant findings to the practice of oncology. For example, Joseph Roscoe, Ph.D., a research associate professor at the James P. Wilmot Cancer Center has led studies that have shown that when patients expect to get nauseous, they often experience worse nausea than people who do not expect it. The expectation is usually associated with a persons prior experiences, such as a tendency to get motion sickness, or to become nauseous when pregnant.

Another study, presented at ASCO in 2009, concluded that people with cancer could reduce post-chemotherapy nausea by using ginger supplements, along with standard anti-vomiting drugs, before undergoing treatment.

Roscoe is now leading a team launching a large study across upstate New York, in a continuing quest to help cancer patients cope with nausea during chemotherapy by using relaxation techniques and acupressure wrist bands. An earlier clinical trial provided the pilot data needed to secure a $2.9 million grant, awarded by the National Center for Complementary and Alternative Medicine for the five-year project.

Studying and Reducing Side Effects of Treatment

While the number of cancer survivors in the United States has tripled since 1971, gains in survival have come at the price of second malignancies and cardiovascular disease, according to a report by a national scientific committee chaired by URMC's Lois B. Travis, M.D., Sc.D., and published in March 2012 in the Journal of the National Cancer Institute. Travis is internationally known as a leading long-term researcher in cancer survivorship, based on decades of groundbreaking work at the National Cancer Institute.

For many survivors the successes of treatment have been offset by the late effects of cancer and its therapy, said Travis, a professor in the Department of Radiation Oncology and director of the Rubin Center for Cancer Survivorship at the James P. Wilmot Cancer Center at URMC. Although many complex factors influence the risk of second malignancies and other health issues after cancer treatment including lifestyle choices such as diet, exercise, alcohol and tobacco use, as well as genetics, age, and immune system function it is vital that we develop the best possible long-term risk estimates and prediction models, and that we establish research priorities and identify concrete ways to prevent serious additional health problems among cancer survivors.

The focus of the committee, which was assembled by the National Council on Radiation Protection and Measurement, was on the long-term consequences of radiation therapy, which is a cornerstone of cancer treatment and used in approximately 50 percent of all cancer cases. (Chemotherapy was addressed to a lesser degree, when used in combination with radiation. In October 2012, a study led by Travis, as Principal Investigator, was awarded a $5.8 million grant by the National Cancer Institute (NCI). The grant is funding a new, multi-center study of cancer survivors that could lead to ways to identify patients who are more susceptible to experiencing long-term and debilitating side effects from a common and effective chemotherapeutic agent.

Travis and her study collaborators at other U.S. cancer centers and an additional center in Canada will spend the next five years studying nearly 4,000 testicular cancer survivors who were treated with cisplatin-based chemotherapy. It has been estimated that a sizable proportion of patients treated with cisplatin-based chemo may experience hearing loss or constant ringing in the ears, another 30-40% sensory neuropathies (or nerve damage), and still others decreased kidney function. The objective of the researchers is to evaluate genetic susceptibility to long-term platinum toxicity. This study population is composed of testicular cancer survivors, most of them cured of cancer, and is considered ideal for examining the genetic underpinnings of long-term platinum toxicity given their typically young age at diagnosis, high cure rate, and possible lifelong risk of treatment side effects.

Protecting Hearts of Childhood Leukemia Survivors

About 75 percent of children with leukemia who receive chemotherapy face life-threatening heart problems as they age, but an international study led by a University of Rochester Medical Center investigator shows that giving a cardio-protective drug during cancer treatment may prevent the damage.

Led by Barbara L. Asselin, M.D., professor of Pediatrics and Oncology at URMC, the study was sponsored by the Childrens Oncology Group and the National Cancer Institute. It is believed to be one of the largest trials to evaluate the effectiveness of the drug Zinecard (dexrazoxane), at protecting the heart during treatment of acute lymphoblastic leukemia.

Today the majority of children with leukemia will be cured, Asselin said. As our young people survive, though, we believe we will see many more cardiac issues. It is a problem that must be fixed because it is the leading cause of death later in life among these patients.

We now have some very effective cancer treatments at our disposal but we really need to focus on promoting the good health of our survivors. Our care does not end with chemotherapy. Being there for many years into the future, and to help childhood survivors understand their risks, is so important.

Preventing Late Radiation-Induced Effects

Improving our ability to prevent injury affecting healthy tissues of cancer patients treated with radiation therapy is a central research goal at the Wilmot Cancer Center led by Principal Investigator Jacqueline P. Williams, Ph.D., research professor in the Department of Radiation Oncology. A $15 million, five-year award, received August 1, 2010, from the National Institutes of Health/National Institute of Allergy and Infectious Disease allows URMC research teams to focus on testing the ability of known drugs and experimental agents particularly antibiotics, antioxidants, and anti-inflammatories to ward off systemic radiation injury that affects the lungs, brain, skin, immune system and bone marrow.

For decades we have built an expertise here in looking at the delayed effects of radiation exposure, mostly in the context of cancer treatment, Williams said. The most exciting part of this project is that through these and other collaborative efforts, we believe we are at the brink of discovering ways to mitigate the damage caused by radiation and protect the body from the repercussions that can arise months or years after the exposure.

Cancer patients will benefit from this project, as researchers uncover new information about how to reduce side effects, such as a loss of brain function that can result from chemo and radiation therapy or how to protect blood vessels and bone marrow from radiation injury. The URMC investigators will be working closely with industry partners to test emerging drugs in this area.

Many of the known drugs and experimental agents that we are testing have the potential to reduce the side effects of cancer treatment without adding new toxicities, Williams said.

With a new clinical survivorship now in place at Wilmot and serving as a logical extension of their work, the energy of survivorship researchers is rekindled. With the creation of the clinical program, these researchers are poised for new discovery, and training the next generation of scientists.

Dialogue Spring 2013 Cover

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