STANFORD, Calif., - Parents of children with brain tumors face an excruciating dilemma. Radiation necessary to kill life-threatening tumor cells can also damage normal brain tissue, resulting in permanent learning disabilities, memory problems and loss of motor control.
Physicians at Lucile Packard Children's Hospital at Stanford are now testing a new treatment that uses less radiation and more chemotherapy than conventional therapy. The study is part of a nationwide clinical trial aimed at preventing brain damage while treating medulloblastoma - the most common malignant brain tumor in children.
"It's double jeopardy for these families," said Paul Fisher, MD, assistant professor of neurology, pediatrics, and neurosurgery at Stanford University and Packard. "They have to deal not only with the fact that their child has cancer, but also that the treatment itself can hurt their brain." Because children's brains are still developing, long-term damage from radiation is more likely and more severe than that seen in adults receiving similar doses.
Packard is the only hospital west of Pennsylvania participating in the Phase II trial, which aims to enroll 50 children nationwide. About 25 children per year are diagnosed with medulloblastoma in Northern California, and about 20 of the trial's patients will be enrolled at Packard. Fisher, the trial's principal investigator at Packard, is about to enroll his third patient.
Brain tumors are the second most common pediatric cancer, and are the leading cause of disease-related death in children. Medulloblastomas account for 20 percent of childhood brain tumors - or 500 cases per year nationwide. The trial singles out medulloblastoma patients for treatment because the tumor is both common and curable; over 80 percent of average-risk children - those undergoing complete tumor removal with no evidence of tumor spread - are alive five years after their diagnosis. But the necessary treatment can also come at a devastating cost.
In the early 1990s, standard treatment for medulloblastoma called for 3600 cGy or rads (units of radiation), to the whole brain and spine, and even more to the cerebellum, where medulloblastomas are located. But even though this dose of radiation alone was often successful in eradicating the tumor, patients almost inevitably suffered severe neurological impairment as a result.
"Any child under seven who receives this dose of radiation to the head and spine is guaranteed to be in special education classes," said Fisher. Children are likely to suffer from memory problems and difficulties in visual motor processing, quantitative reasoning and understanding spatial relationships.
In an effort to protect the normal brain tissue from destruction, children are now normally treated with a dose of 2380 cGy, supplemented with several rounds of chemotherapy - a combination that gives equivalent survival rates as the higher dose of radiation alone. But the majority of these patients still come away with some degree of impairment, according to Fisher. "It's becoming clear now that even though this is a step in the right direction, these kids are still significantly affected," he said.
The current trial is designed to test whether 1800 cGy - combined with one extra round of chemotherapy - will be enough to conquer the tumor without damage to surrounding brain tissue. "The reason we're so excited is that children with leukemia who received this dose of radiation to their heads and spines to prevent metastases show that they maintain pretty close to normal neurological function," said Fisher. "And, seven out of 10 kids with medulloblastomas treated with 1800 cGy during a pilot study in the late 1980s are alive today. It would be so wonderful to be able to approach a family and say 'We're going to treat your child, and there are no strings attached,'" said Fisher.
The new treatment protocol calls for the patients to receive a total of 1800 cGy over the course of six weeks to the head and spine, with a boosted dose to the tumor itself. After a four-week break, patients begin nine cycles of chemotherapy, separated by six-week intervals. To volunteer for the trial, call pediatric neuro-oncology nurse practitioner Ruth Rosenblum at 650-723-7133.
In addition to Packard, the Children's Hospital of Philadelphia, New York University Hospitals, and Children's National Medical Center in Washington, are participating in the trial.
Lucile Salter Packard Children's Hospital at Stanford is a 240-bed hospital devoted entirely to the care of children and expectant mothers that is celebrating its tenth anniversary in 2001. Providing pediatric medical and surgical services associated with Stanford University Medical Center, Packard offers patients locally, regionally and nationally with the full range of health care programs and services - from preventive and routine care to the diagnosis and treatment of serious illness and injury. To learn more about Lucile Packard Children's Hospital, please visit our Web site at http://www.lpch.org