Diagnostic And Treatment Program For Children With Brain, Spinal Cord Tumors Opens At Cedars-Sinai

In addition to giving patients access to therapeutic trials that may be available at no other center in the nation, the Pediatric Brain Tumor Program at the Maxine Dunitz Neurosurgical Institute will offer a comprehensive, supportive approach to care that transcends the typical disjointed referral process.

Specialists in pediatric oncology, neurology and endocrinology, neuroradiology, radiation therapy, neuropsychology, genetics, and a range of other disciplines will collaborate with the patient's primary care physician. Together, they will develop a well-orchestrated plan to ensure continuity of care from diagnosis, through therapy and into reintegration at school and long-term follow-up.

"I think one thing that distinguishes us is the depth of comprehensive care that we're able to provide," said Paul M. Zeltzer, M.D., a specialist in pediatric neuro-oncology who has directed international clinical trials of treatments for the most common childhood tumors.

"We don't see our program ending with the individual patient," said Dr. Zeltzer. For example, Cedars-Sinai's expertise in genetics research and counseling will help provide unique cancer service for the entire family.

"In taking a family history on a child who has a brain tumor, for instance, we might find that there's a grandfather with early colon cancer and a cousin with endometrial and ovarian cancer. This pattern suggests a specific syndrome," said Maren Scheuner, M.D., director of Cedars-Sinai's GenRISK Program. "If we get that positive history, we will involve the counseling team because there may be other extended family members at risk. Early detection would be very important in that family and in the extended family group."

For children with genetic-based neural tumors like those seen in neurofibromatosis or tuberous sclerosis and others, Julie Korenberg, M.D., vice chairman of Pediatrics, and Stefan Pulst, M.D., director of the Division of Neurology, lead one of the largest multidisciplinary neurogenetics teams in the country. They emphasize that the lessons learned from these genetic tumors may well provide the critical clues to understanding and ultimately treating brain tumors in general.

Treatment for a brain or spinal cord tumor often includes several kinds of therapy, including surgery to remove the tumor, followed by radiation and/or chemotherapy to attempt to destroy any remaining cancer cells. A recently completed study points out the value of the neurosurgeon's skills in affecting long-term survival rates.

"We've learned that the 'quality' of the neurosurgery turns out to be very important. By that, I mean not just the gentleness of how the brain is handled to prevent long-term effects of brain damage, but actual removal of the tumor," said Dr. Zeltzer. "We found that if the neurosurgeon was able to leave less than 1.5 cc (cubic centimeter) of tumor, there was a 25 percent survival advantage. In other words, if the surgeon could leave less than 1.5 cc, 78 percent of the children survived at least seven years. If the surgeon left more than 1.5 cc of tumor, the rate dropped to 55 percent. So the actual 'behavior' of the neurosurgeon in the operating room can set the stage for the likelihood of a relapse two, five or seven years later. Fortunately, the Neurosurgical Institute is the premier facility in terms of the quality of neurosurgery -- ensuring the removal of as much tumor as can safely be removed."

The study was conducted in conjunction with the Children's Cancer Study Group, and involved more than 400 patients and 40 institutions in the United States, Canada and Australia. An article on the study, authored by Dr. Zeltzer, has been accepted for publication in an upcoming issue of the Journal of Clinical Oncology.

"Twenty years ago, before the more comprehensive oncology care was introduced, children might receive radiation and no chemotherapy for some of the common brain tumors," said Carole Hurvitz, M.D., director of Pediatric Hematology-Oncology at the CSMC-Comprehensive Cancer Center and team member. "Survival rates in some of those tumors have gone from less than 20 percent to over 70 percent. That's seven-year survival, which may not be 'cure' but it's certainly on the way to cure."

Looking at recent trends in diagnosis and treatment, there are reasons for optimism, despite the fact that numerous challenges remain. "The bad news is that the incidence of brain tumors in children appears to be increasing gradually," said Dr. Zeltzer, noting that some experts believe this may actually be the result of improved diagnostic technologies. The good news is that today's children with tumors of the brain or spinal cord have greater hope of long-term survival and possibly cure than did those in decades past, although outcomes depend on many factors, including the type and stage of cancer, and the institution where they are treated.

One of the keys to successful treatment is correct diagnosis, which emphasizes the value of a comprehensive program offering state-of-the-art imaging and neuropathology facilities plus a highly respected research team. "We diagnose several hundred adult and pediatric brain tumors each year. This challenging task is eased by technical innovations including flow cytometry and electron microscopy laboratories," said neuropathologist William Yong, M.D. "Unless the patient is at an institute that's using very sophisticated techniques, children could receive inappropriate therapy based on inaccurate diagnosis. In addition, we are committed to studying genetic alterations in brain tumors and their potential role in improving diagnostic capabilities."

Even under the most favorable conditions, the prognosis for many brain tumors is uncertain, and treatment options are limited. "We're trying all the time to develop new and better treatments and improve upon what we already know," said Dr. Zeltzer, who was among the first specialists about 15 years ago to reconsider the use of radiation therapy in treating children with brain tumors. Because radiation can cause damage to the developing brain, researchers are hoping hyper-intensive chemotherapy will continue to reduce the need for radiation.

"We developed very intensive chemotherapy regimens, and for infants with leukemia of the nervous system, we wound up improving their survival rates remarkably. But we've learned that brain tumors in young children are very aggressive," said Dr. Hurvitz with Dr. Zeltzer's agreement. "Although we can halt the tumor in about 20 percent of cases with chemotherapy alone, it isn't effective enough in the other 80 percent." Children in the Pediatric Brain Tumor Program will be able to participate in therapeutic trials developed at Cedars-Sinai as well as those sponsored by the National Institutes of Health, the National Children's Cancer Study Group and other programs.

"Hyper-intensive chemotherapy with bone marrow rescue or stem cell rescue are among the new tools being tested against some tumors," said Dr. Hurvitz. In these procedures, specific types of blood cells are collected from the patient and frozen. After the administration of a course of chemotherapy designed to destroy all cancer cells, the collected blood cells are thawed and reinfused into the body, where they mature into new bone marrow cells, replenishing those lost to the power of the drugs.

"Following therapy, many children may need hormone replacement to continue their growth or enter puberty," said Naomi Neufeld, M.D., the team's pediatric endocrinologist. "Because weight gain after treatment can be a problem, they need specialized services offered here at Cedars-Sinai."

"Another approach we're developing is immunotherapy. The Maxine Dunitz Neurosurgical Institute here, under the Direction of Keith L. Black, M.D., is one of the country's pioneers in developing immunotherapies for brain tumors," according to Dr. Zeltzer, who joined the Cedars-Sinai medical staff this past August. The Tumor Vaccine Program uses the patient's own immune system in an effort to control and destroy tumor growth.

John Menkes, M.D., emeritus professor of pediatrics at UCLA, director of Pediatric Neurology at Cedars-Sinai, and author of the often-quoted "Pediatric Neurology" textbook, said, "Parents should be alert to several signs that are sometimes associated with brain tumors: a change in personality or behavior that is out of character for a child; vomiting -- especially morning vomiting that continues for more than a week; and seizures, which in children are only occasionally related to a brain tumor."

"Headache is the most predominant symptom," said Dr. Menkes. "A headache in a child younger than 5 years of age is never a tension headache and should always be looked at as a sign of something more serious. It may be sinusitis, another illness or possibly a brain tumor, but young children do not get tension headaches."

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For information about the Pediatric Brain Tumor Program, call 310-855-7900.