As one of the first brain tumor research and clinical programs in the United States, the Preston Robert Tisch Brain Tumor Center at Duke is paving the way for pediatric and adult neuro-oncology programs around the world. At the helm of this staff is a team of physicians who have made it their mission to ensure that malignant brain tumors are curable in the future. They are internationally recognized, not only for their groundbreaking research, but also for their commitment to fostering hope among patients and families who are afflicted with neurological diseases. “We believe hope is the foundation of everything we do,” says Dr. Henry Friedman, a neuro-oncologist and co-director of the Tisch Center. “Even with the worst brain tumors, whether you are successful or not, hope is the fountain from which everything springs.”
The Evolution of the Tisch Center
“There wasn’t a formal brain tumor center when I came to Duke in 1963,” explains Dr. Darell Bigner, co-director of the Tisch Center and director of the Pediatric Brain Tumor Foundation Institute at Duke. “But the first neurosurgeons had established both clinical and research programs, and that’s what attracted me to Duke — their national and international prominence.”
Duke didn’t establish the Tisch name until 2005, thanks to generous donations from the family of Preston Robert Tisch, chairman of Loews Corporation and co-owner of the New York Giants, who was treated for a brain tumor at Duke. Since then, the work of Dr. Bigner and that of Dr. Henry Friedman and Dr. Allan Friedman have continued to grow Duke’s neuro-oncology programs, applying Tisch funds to support research studies and clinical trials that have resulted in the first new treatments to be approved for brain tumors in more than a decade.
Dr. Bigner says that when he first started, there were “no good imaging studies for diagnosis, no good drugs that worked for edema and swelling, no chemotherapy and we didn’t know how radiation worked. All of these things have happened since the late 1960s and have been improved since that point.”
The Impact of Brain Tumors
A diagnosis of glioblastoma multiforme (GBM), or a malignant brain tumor, is devastating news for a patient. According to the American Association of Neurological Surgeons, GBM typically results in death in the first 15 months after diagnosis. But thanks to ongoing efforts at Duke, GBM isn’t necessarily a death sentence. In 1985, fewer than 25 percent of patients lived five years with brain cancer. Today, the five year survival rate is approximately 35 percent, and patients are surviving 10 and even 15 years past their initial diagnosis.
The Tisch Center sees between 900 and 1000 newly diagnosed glioblastoma patients each year, the most common malignant brain tumor in adults. While the disease remains unpreventable, Dr. Bigner and his team believe there will be a greater percentage of patients who are curable. “We have some extremely long-term survivors,” he says. “Today we see 10-year survivors with the most malignant form of brain tumors. The percentage of patients who respond like that will get better in the next few years. I believe that in my lifetime we will see a larger percentage of patients who are cured.”
Like many cancers, conventional treatment for GBM includes surgery to remove as much of the tumor as possible. But surgery is particularly difficult since glioblastoma manifests tentacles that envelop the brain. Because the entire tumor cannot be removed, surgery is typically followed by radiation and chemotherapy. In the last few decades, this has involved the surgeon placing dissolvable wafers made of chemotherapy drugs on or near the remaining tumor.
While this treatment has improved the outcome for some GBM patients, this isn’t good enough for Dr. Friedman and his colleagues. “In the next five to 10 years, I hope to make major steps forward in the cure rate for GBM,” he predicts. “There are a lot of new strategies that can be employed to give us a better outcome.” This is why Duke physicians often deviate from standard care if there is a chance of improving a patient’s chance of survival.
Instead of trying a new therapy only after another one fails, they evaluate each patient’s unique case before employing a number of treatments at the same time. This often involves approved therapies, but often a patient will undergo a clinical trial as well. (At Duke, more than 66 percent of adult patients and 75 percent of pediatric patients are enrolled in clinical trials.)
In recent years, the Tisch Center has unveiled CDX-110, a vaccine developed by Duke neurosurgeon Dr. John Samson. The vaccine “trains” immune-system cells to attack EGFRvIII, a protein that is present in 25 to 40 percent of GBM patients. The results of the clinical trials of this vaccine were so successful (it doubled the survival time of patients) that Duke licensed the vaccine to the pharmaceutical company Pfizer.
For recurrent glioblastoma, Duke researchers have made significant progress with the anti-cancer drug Avastin, which prevents the tumor from growing new blood vessels to support it. “Dr. James Vredenburgh played a pivotal role in the approval of this drug that had previously been used to treat lung and colorectal cancer,” Dr. Friedman says. ”It’s now one of the mainstays for GBM.” In a study conducted by a team that included Dr. Friedman, Dr. Vredenburgh and Dr. Bigner, Avastin nearly doubled expected survival to six months. The FDA approved the drug for GBM in 2009, making it the first new treatment approved for this disease in more than a decade.
“There are many more new treatments being developed,” Dr. Bigner says. “There are a large number of vaccine studies in clinical trial, and an immunotoxin for targeted cancer therapy.” An immunotoxin, or a protein that contains a toxin along with an antibody, binds to a surface on a cancer cell and kills it. “We’re also looking at DNA repair mechanisms to remove mutations, and we have a very active epidemiology group here at the Center,” he says. “We will continue to develop cutting edge methods of diagnosis and treatment and continue to see long-term survivors.”
The Cost of Finding a Cure
While GBM is one of the most common forms of brain cancer, it is still a relatively rare disease, causing just two percent of all cancer deaths each year. Consequently, the federal government classifies it as an “orphan disease,” and because public research funding is allocated based on the incidence of a disease and not the mortality rate, the Tisch Center depends on research grants and donations to cover their costs.
With more than 120 types of brain cancers, each with different chemical profiles, it is difficult to locate funding for clinical investigations of each one. As a result, Duke orchestrates a number of fundraising events throughout the year including the Teddy Bear Ball in December and the Angels Among Us Walk in April (see sidebar).
In addition, individuals can make donations to the Tisch Center anytime of the year. Families of GBM patients can give memorial gifts to honor a loved one, and many employers offer a matching program where the company matches any monetary donation an employee makes to a specific charity. All gifts are tax deductible, and each of these contributions can help in finding new treatments that will improve outcomes for patients and families. Gift forms are available on Duke’s website, www.cancer.duke.edu.
The Future of GBM at Duke
Moving forward, the Center is investing a portion of the most recent gift from the Tisch family in genomics research aimed at developing individualized treatments using a patient’s genomic signatures. “The ability to do complete genome sequencing gives each patient’s tumor an individual blueprint of what has gone wrong,” Dr. Bigner says. “It can be done fast enough and cheaply enough, and it’s now entering our clinical practice.”
And while there is always the hope of finding a form of prevention for GBM, there is only one known cause, and that is radiation exposure from the treatment of different types of cancer. Now that doctors have identified this, it can be prevented, but this only affects less than one percent of cases.
In the meantime, Duke will continue research to identify more causes of GBM, both external and internal, as they work to make new therapies available to their patients. “At Duke there is hope,” Dr. Bigner says. “Patients are told that even though this is a serious problem, there are things to be done, and we will try all of those things. It is not a hopeless situation. Even with most malignant types, there are long-term survivors.”
ANGELS AMONG US
April 20, 2013 marks the 20th anniversary of the annual Angels Among Us Walk. The event draws thousands of participants — patients with brain or spinal tumors, their family members, caregivers, as well as physicians and researchers involved in new treatments and clinical trials. The first event in 1994 raised $27,000. Last year, Angels Among Us raised $1,802,475.
The event begins with a 5K run through the Duke campus, followed by a Family Fun Walk through the Sarah P. Duke Gardens. It has a family-friendly focus with entertainment, food, raffles and activities and prizes for children. The day concludes with a closing ceremony where the top 10 fundraising teams receive an award and the grand total raised for the event is announced.
Registration for the 2013 Angels Among Us Walk is officially open, setting a goal to raise $1,900,000. Visitors are asked to click on the participant page and begin inviting friends and family to join their team and start the fundraising process. For more information, visit www.angelsamongus.org.