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Releases Packard
Children's News
Children's Fund
Update |
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The Dark Realm of Brain Tumors
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| Casey Mackin was diagnosed with a fast-growing medulloblastoma during her junior year in high school. |
In January 1999, about two weeks before her departure date, Casey started getting headaches and vomiting in the mornings. Her family doctor in King City, Calif., initially thought it was a sinus problem. Then, on a farewell snowboarding trip only days before her flight, the normally agile 16- year-old was bizarrely uncoordinated, crashing her board into trees and staggering into astonished friends.
In the hospital emergency room back home, her doctor ordered brain scans, which revealed the cause. A tumor called a medulloblastoma had reached the size of a small lime and was pushing on her brain, causing tissue inflammation and fluid build-up. Casey urgently needed specialized surgery to remove the mass and relieve the pressure, followed by months of radiation and chemotherapy to destroy any remaining cancer cells. Doctors referred her to Packard Children's Hospital, which had launched a specialty clinic for kids with brain cancer.
Casey wasn't frightened at first. She was furious.
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Research: Seeking the Seeds of Cancer |
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Research: Shrinking the Effects of Radiation |
"When they told me I had a brain tumor, I remember thinking, 'What do you mean—no Costa Rica?' It wasn't like, 'I could die.' I was just so mad!" she recalls.
Two hours to the north of King City, in San Jose, a 6-year-old girl had a bad case of flu, or so her pediatrician thought. But after more than a month of intensifying headaches and lethargy, Mikaela Clifford was barely conscious and had to be rushed to the emergency room. CAT scans turned up a tumor, coincidentally quite similar to Casey's. A doctor in the ER took Mikaela's mother aside and said, "Pace yourself. It's going to be a long road."
Casey and Mikaela were strangers then, but they would soon become inseparable. Traveling together through the dark realm of brain cancer, they would inspire and comfort each other, and crack each other up, until tragically, in the end, their courses diverged.
Brain cancer sneaks up on a child like a monster under the bed. Lurking in its shadowy niche, it stays hidden until it's big enough to cause an all-out crisis. Not only is a brain tumor out of sight, but it's also out of reach of many treatments that work against other types of cancer. It can steal a child's very essence by disrupting the development of the mind, making it potentially the most life-altering of all pediatric cancers.
It is also the deadliest. In fact, no other illness—cancerous or otherwise—kills more children in the United States today.
Now, through the creation of a new Center for Children's Brain Tumors, clinicians at Packard Children's Hospital and basic scientists at the Stanford School of Medicine are joining forces to apply new insights to the pediatric brain. By taking a multi-disciplinary approach to research and the development of treatments, they intend to improve the outlook for every afflicted child, and to establish unequivocal cures.
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Neurosurgeon Michael S.B. Edwards, M.D., an expert in developing treatments for children with brain tumors, joined Packard's neurosurgery team in 2004. |
"Many people think brain tumors are very rare, when they're the most common solid tumors of childhood," says Michael S.B. Edwards, M.D., a world renowned pediatric neurosurgeon recruited to Packard in 2004. "Leukemia is still slightly more common, it's true—but today we cure leukemia 80 percent of the time, and we don't do that for brain tumors."
Thirty years ago, leukemia was the dreaded childhood cancer, with barely 50 percent odds of survival. Over the last several decades, concerted research efforts have led to effective drugs, significantly increasing the percentage of children who recover from leukemia.
Kids with brain tumors faced a similarly dismal outlook 30 years ago, but their survival rate today is only slightly improved, at around 60 percent, although rates vary significantly depending on the type of tumor.
What starts a brain tumor growing in a child? Are some of its cells more cancerous than others? Could a cancer cell ever go back to being normal? Why would a treatment work in one child but fail in another with the same kind of tumor?
Questions like these have puzzled brain specialists for decades. Now, thanks to advancements in molecular and developmental biology, the answers are tantalizingly within reach.
"I have a fire in my belly that it's time to get this done," says Edwards. "Scientists have made incredible strides in molecular biology, which means we're beginning to understand how cells function at the most basic level."
In a career spanning three decades, including serving on the faculty at UCSF and UC Davis, and most recently as director of the Sutter Neuroscience Institute in Sacramento, Edwards has been a leader in developing innovative treatments for children with brain tumors. He was lured to Packard and Stanford by the opportunity to work with great minds from many different disciplines.
"At Stanford, we've got all these very key, bright people who didn't come here to cure pediatric brain tumors but whose work is highly relevant to brain tumors," Edwards says. Stanford has enormous strengths in the basic biological sciences and in advanced technologies like genomics, proteomics, stem cell biology, and functional MRI. "We want to get all these people working with each other, tackling problems together from different angles."
The Center for Children's Brain Tumors will be one of the first programs associated with the interdisciplinary Neuroscience Institute at Stanford, recently established by the School of Medicine to create a new culture for speeding the discovery of disease mechanisms and translating them into cures. On the clinical side, Packard Hospital contributes strengths of its own, including advanced surgical capabilities and an outstanding medical program that develops and participates in breakthrough clinical trials.
"So we have this two-way street going here," says Edwards. "If, God forbid, you had a child with brain cancer—this is where you would want to be."
Institute director William Mobley, M.D., Ph.D., chair of the Department of Neurology and Neurological Sciences at Stanford, notes that: "progress in neuroscience today takes new ways of thinking together and working together, and new methods to support collaboration among doctors, scientists, patients, and industry."
Most kids diagnosed with brain tumors need surgery within days, because the mass is putting pressure on the brain. There's no time for reflection until that crisis is resolved. The brief phase between diagnosis and surgery can seem surreal for both children and families.
Currently, surgery is the single most effective therapy in altering the prognosis for pediatric brain cancer. A highly skilled neurosurgeon working with state-of-the-art technology can make all the difference in the outlook for a child.
"You need to be able to develop very good relationships with children and their families," says Stephen Huhn, M.D., Packard's chief of pediatric neurosurgery, who has been a leading force in the development of the Hospital's neurosurgery program over the last eight years.
In Edwards and Huhn, Packard Hospital has two board-certified pediatric neurosurgeons; other neurosurgery programs are lucky to have one. Rarer still is the fact that they share a strong interest in brain cancer.
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Mikaela and Casey |
Removing children's brain tumors requires highly specialized training and some of the riskiest and most difficult procedures in all of surgery. "It can be extremely challenging," Huhn says. "It takes a lot of concentration over a very long period, maybe four to eight hours. It takes a lot of courage."
Notes Edwards, "Operating on a day-old baby is very different from operating on an adult. We're also dealing with the complexities of growing, developing people. From newborn to age 19, their physiology differs, their types of tumors differ. Their biology and support needs are totally different."
In addition to its multidisciplinary approach and concerted clinical program, what is critical, says Edwards, is Packard's leading edge in surgical technology.
Advanced endoscopic techniques give the neurosurgeons a minimally invasive way to sample tissue in order to diagnose certain deep-seated brain tumors. And two new "navigational" techniques assist in removing tumors without harming critical tissues elsewhere in the child's brain. One of these, called MRI-guided frameless stereotactic navigation, is useful during surgery to assist in locating and agressively removing tumors. The other technique, so new that only a few hospitals have obtained it so far, is a realtime feedback system called intraoperative MRI. It monitors and displays anatomic positions in the tumor and brain as surgery is taking place. Linked with image guidance, it dramatically improves the precision and safety of the procedure. Hospital investment in the Center for Children's Brain Tumors includes bringing this new technology to Packard.
The nationwide increase, albeit modest, in recovery rates for childhood brain cancer stems mainly from surgical innovations introduced in the past decade or so. But surgery, in itself, may have reached its limits, since it cannot remove microscopic cancer cells that may have infiltrated surrounding tissues in the brain.
"The best brain cancer therapies of the future will probably have nothing to do with surgery. They'll probably be genetic therapies," says Edwards. "And wouldn't that be great? I've said it a million times: The best thing I could do in my surgical career is put myself out of business."
The girls first met in the radiation department. Casey was coming in for her daily treatment; Mikaela was on the way out from hers. The 6-year-old lay in a red wagon pulled by her mom. Bare patches showed through her long brown hair; Casey had already shed so much that she had asked a barber to shave the rest off.
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| Casey "lives and loves it up." |
The older girl knelt down and pointed to the little one's nasogastric tube. "Oh, you have that thing, too? The one where you think they're gonna put it down your throat, and then you close your eyes and they shove it up your nose?" Mikaela erupted in commiserative giggles and they became instant friends.
"All through the radiation and chemo, we would spend our time together being funny and laughing," recalls Casey. "Live and love it up—that was Mikaela's motto. When they would try to get us to do stuff we didn't want, we would be like, 'Shoot! That stinks! Why don't we just leave?' Then she would laugh and say, 'No, we’ve got to do it.'"
In May 2000, when the treatments were finished, their parents threw them a party. "We had all changed," recalls Isabel Rosales, Mikaela's mom, "but we were so thankful to be moving on." Mikaela lived and loved it up at Camp Okizu, a festive retreat for kids who've had cancer, while Casey and her family trekked through Costa Rica.
That's what neuro-oncologist Paul Fisher, M.D., told himself in 1997, when, having established himself as a rising star at Johns Hopkins Medical Center in Baltimore, he went west to create a clinical program devoted to children with brain cancer.
That was at the heady peak of Silicon Valley's high-tech boom. "I came to Stanford and Packard Children's Hospital because of the conviction that you can build things here, that you can make things happen," says Fisher, a Stanford undergraduate alum and now the Beirne Family Medical Director of the Center for Children's Brain Tumors. "I wanted to see what could be done in a setting that is truly patient-based, but with a strongly academic, multidisciplinary bent—a place that is team-based instead of pyramidal and where you’re not tied to your departmental lines."
A large population in the South Bay needed the services of a child-oriented brain cancer clinic. But when he first built the program, they didn't come automatically.
"I would have my weekly clinic day and there would be maybe one patient," Fisher recalls. "The others were still traveling up to UCSF, Sacramento, or Oakland for treatment, or going to adult oncology clinics in the South Bay."
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| Packard neuro-oncologist Paul Fisher, M.D., examines 5-year-old Leah Monsivais of Salinas. Fisher has developed one of the region's most successful clinical programs to treat children's brain tumors. |
The quiet didn't last, of course, as word spread and more doctors began sending their young patients to the program. Patient volume has increased steadily, and the clinical program has grown to encompass pediatric neuro-radiologists, radiation oncologists, neuro-pathologists, neuro-psychologists, and other subspecialists, working closely with the recently expanded program in pediatric neurosurgery. Every year now, more than 60 kids with newly diagnosed brain tumors come to Packard Children's Hospital. Throughout the state of California, more than 210 such tumors are diagnosed each year.
In fact, so many children with brain cancer are being referred to Packard, from inside and outside California, that some may literally have to wait for beds. "The intensive care unit is log-jammed," says Fisher. "We've got this dream team here wanting to help these kids. New intensive care beds, along with a dedicated operating room for neurosurgery, are thus among the most urgent goals of the new Center."
When surgery is over and the child begins radiation and chemotherapy, the large patient volume, coupled with the hospital's academic setting, brings an enormous advantage: access to a range of clinical trials. The program takes part in every brain cancer trial of the Children's Oncology Group (COG), a National Cancer Institute-supported network for studying experimental approaches to chemotherapy and radiation in children and adolescents. Qualifying kids even have a shot at COG's earliest phase 1 trials, which test the feasibility and efficacy of compounds never before used to treat or cure childhood cancers. "Packard is the only COG early phase 1 institution between Los Angeles and Portland," Fisher says.
In addition to COG studies and other multicenter trials, the neuro-oncology program launches investigations of its own. Fisher is leading a Stanford-only trial of a regimen combining a standard chemotherapy agent with the drug thalidomide. Valued today for its promise against many types of cancer, thalidomide has an effect called anti-angiogenesis, curbing the development of new blood vessels feeding into a tumor. "In devising new treatments for cancer, we want to take advantage of multiple approaches," Fisher says. "Let's say you want to kill the grass in your front yard—you could pour poison on it, you could alter the soil, or you could shut off the sprinklers. In this case, we're shutting off the sprinklers."
Quality of life after treatment is a major concern in pediatric brain cancer. The radiation administered to destroy tumor cells almost always kills some normal cells in the still-developing brain, leaving young brain cancer survivors with cognitive impairment that persists, and may progress, as they mature.
A promising phase 2 clinical trial now being offered to every child in the program with newly diagnosed medulloblastoma reduces the amount of radiation exposure and increases the chemotherapy. The hope is that this regimen will have the same tumorkilling power, but will minimize cognitive impairment.
Even in children who never get radiation, the tumor itself seems to disrupt the brain. "It's a sad fact that kids who survive brain tumors have diminished quality of life, whether they are treated with surgery alone, with chemo, radiation, or any combination of the three," says Fisher. "Like a tree growing up through the sidewalk, the growing tumor distorts structures all around it."
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