The Dark Realm of Brain Tumors
New Center Sheds Light on Deadliest of Childhood Cancers

'You rock, Mikaela.'

One year after the treatments ended, Casey seemed to be thriving at college, unfazed by any side effects other than feeling a little less limber. Mikaela, too, was back at school, where she particularly enjoyed tutoring kindergartners. An extremely bright and energetic kid, Mikaela was thinking more slowly these days and struggling with the loss of her athleticism.

Mikaela visits Casey at college.

Mikaela's brain scan, like Casey's, looked good at the one-year follow-up point. "They told us if it still looked good six months later, things might be in our favor," Mikaela's mom, Isabel, remembers.

Six months later, it didn't look good. That was in November of 2001.

Mikaela expressed mixed feelings about embarking on another round of treatment, but she agreed to give it a try, "not so much for herself but for me," says Isabel.

Casey sent her homemade cards embellished with stickers and drawings. "You rock, Mikaela!" one of them said. On college breaks, they'd have sleepovers, making crank calls and gossiping all night.

"She went through the entire treatment, and we actually started to see some progress," recalls Isabel. "I was thinking, 'Oh my gosh, we could get a miracle out of this.'"

That hope faded in March 2003, when new scans showed the tumors growing again.

By November, after 12 full courses of chemotherapy and an experimental therapy called gamma knife radiation, there was nothing left to do. "I remember Dr. Fisher finally having to tell Mikaela he didn't think he could cure her, and his eyes welling up with tears," says Isabel. "He asked her if she would want to be resuscitated if things reached a certain point. She looked at him and said, 'No, I'll let God decide.'"

Mikaela entered hospice care in May 2004, after awakening one morning with a bad headache and finding she couldn't stand without falling. On Oct. 26, 2004, she died in her sleep—5 1/2 years after learning she had brain cancer and three weeks after celebrating her 12th birthday.

'It will take a coalition.'

In the past, basic investigations in the biomedical sciences would often involve pure research far removed from clinical practice. Physicians and researchers alike are now convinced that the greatest breakthroughs will come not from basic research alone, but by focusing on the interface between basic science and clinical practice. That focus, called translational research, is the driving force of the Neuroscience Institute at Stanford.

One firm believer in cross-disciplinary biomedical research is biologist Matthew Scott, Ph.D., who co-directs a pediatric brain tumor working group with Edwards as part of the Neuroscience Institute. Scott gained fame in the scientific world through pioneering work on the key genes that regulate embryonic growth, which eventually led to questions about the role these same genes play in the development of cancer cells. His research group found that damage to one of the genes under investigation causes medulloblastoma. Scott hopes that knowledge of how this gene works will lead to new therapies to treat this fast-growing tumor.

"Discovering more effective ways to detect, prevent, and treat childhood cancers," says Scott, "will take a coalition between clinicians who understand the diseases, their effects on patients, and the current treatments, and basic scientists who are studying the genetics, cell biology, and development of normal and diseased cells."

The new understanding of the genetic basis of cancer is already producing startling results in animal research. "We can actually construct a mouse with a genetic makeup that makes the mouse develop a tumor, and then we can give back certain things associated with metabolism and cell growth, and the tumor will go away," Edwards says.

Another promising area of research looks at stem cells, which normally give birth to myriad kinds of cells in the body and play an essential role in normal development. Some researchers think that brain tumors may arise from "cancer stem cells," a phenomenon being studied by neurosurgeon Stephen Huhn, M.D.

The research on stem cells also has become part of the struggle to save children's cognitive abilities after treatments for brain tumors. Packard researchers Theo Palmer, Ph.D., and Michelle Monje, M.D., Ph.D., have found that radiation interferes with the development of certain cells crucial to normal brain growth in children, and are studying ways to prevent the problem.

Although genes play a decided role in the development of brain tumors, no one has closed the book on environmental contributors. The trick is teasing out the relationship between genetic, developmental, and environmental risk factors. "Cancer is probably a combination of a wrong gene in the wrong place, many times over," says Fisher. Packard is trying to get support from the National Cancer Institute to fund a massive statistical epidemiology study of brain tumors in California. "Nothing like this [study] has been done in childhood cancer on this scale anywhere in the world," Fisher says.

Such wide-ranging research is destined to pay off, Edwards says.

The goal is "targeted therapy based on the molecular biology of the cancer cell," says Edwards. "We are at this point in medicine where we have tools that we didn't have 10 to 15 years ago to develop specific therapies targeted directly at cancer."

'Life is about living it.'

Casey's joy for life grew out of the journey she shared with Mikaela. Now a senior in college, Casey is majoring in education, with a minor in art.

A few days before Mikaela died, Casey was pronounced disease-free. The 22-year-old college senior later spoke eloquently at Mikaela's memorial service, and then returned to school to create a riveting piece of performance art and sculpture that summed up her hospital experience.

In contrast to some younger brain cancer survivors, Casey seems to be moving forward with enormous enthusiasm and vigor.

Casey says her friendship with Mikaela had a lot to do with that outlook. "Both of us went through a big change in life, but Mikaela gained the wisdom of a really old person. While other kids were out running around free as a bird, she was stuck in this body that was deteriorating and she wasn't able to do anything about it—and she found a way of accepting this and kind of going along with it. It didn't inhibit her; it didn't stop her from loving people and letting them know they were special.

"I learned from Mikaela not to complain, that life is just about living it."

Casey's focus right now is finishing college. She's majoring in education with a minor in art. This summer, she hopes to counsel children with cancer at Mikaela's favorite hangout, Camp Okizu. In the longer run, she has an adventurous new dream: to teach elementary school in Costa Rica.

'I don’t want to see another kid die.'

The story of Casey and Mikaela chronicles the challenges of treating pediatric brain cancer today and the courage of children beset with this illness. Like any human tragedy, it also raises excruciating questions.

How is it that one lived and the other did not?

"Both of these girls were incredibly compelling patients. They would run up and hug you, and you always wanted to hug them back," Fisher says. "How can you take these two wonderful kids with the same disease, the same initial treatment—one you can cure, but the other you're handcuffed in your efforts to save? It's painful to think that we played every card we had for Mikaela, and there was nothing more we could have done."

In reality, the form of each girl's disease probably didn't have the same molecular fingerprint. Medulloblastoma, astrocytoma, and other brain cancer diagnoses are actually more like categories than specific tumor types, says Fisher. Scientists have yet to identify the subcategories and find the treatments that work best in each case.

If Mikaela had been born later, she would have benefited from the Center for Children's Brain Tumors.

"Twenty-five years down the road," says Fisher, "we want to be able to say, 'Because of the targeted treatments developed at this center, kids are alive today who otherwise would have died. And survivors are living better lives because we’ve found ways to protect them from cognitive damage.'"

"It's the strength of the kids in the hospital that fires you," Edwards adds. "They ask for so little, like six more months to live. A kid will think, 'I'll put up with that miserable chemo if I get to go to Disney World.' And when you lose a child, it makes you work even harder to learn everything you can. This attitude— learning from every loss in order to help other children— seems to help the parents, too.

"The kids and their families give you the strength to say, 'You know, we have to figure out a cure for this. I don't want to see another kid die from brain cancer. That's it."