by Jon Nalick

In the 50 or so years that scientists have waged war on cancer, frustratingly little progress has been made on brain tumors, but clinicians and researchers at USC/Norris Comprehensive Cancer Center and Hospital have been striving to change that.

Since the USC/Norris opened nearly 20 years, physicians have been at the forefront of neurosurgical advances in an effort to expand treatment options for people afflicted with central nervous system tumors. They have introduced tools and concepts that have altered approaches to brain cancer worldwide.

Now a phase of development, based on this foundation of accomplishment, provides a program that combines surgical, radiotherapeutic and chemotherapeutic approaches to fighting brain cancers. Doctors work together to provide patients with the most appropriate and improved care and the widest array of support services with an eye toward extending patients' lives and bolstering their quality of life.

"When a patient with a brain or spinal tumor comes to USC, options exist for surgery, conventional radiation or Gamma Knife radiosurgical treatments, medical oncology, chemotherapy or clinical trials," says Thomas Chen, M.D., Ph.D., assistant professor of neurological surgery, who co-directs the program. "In addition, an internist can evaluate the patient for general medical problems and, if social support is needed, there's a psychologist available, as well as rehabilitation specialists."

Having all those services available is crucial because of the serious nature of the disease and the swiftness with which it can progress, even with appropriate treatment.

"Unfortunately, the most common brain tumors are cancerous, and there's currently no cure for them. For malignant gliomas, survival from the time of diagnosis is just two to three months if no treatment is given. With treatment, survival is only increased from about six to eight months back in 1970 to about 10 to 12 months today," Chen says.

The slow progress against the disease underscores the intractable nature of the illness and the challenges in overcoming it.

Chen notes that treating brain tumors is especially difficult because of several factors. One is that brain tumors are often surgically inoperable simply by virtue of their location or because they have already invaded nearby parts of the brain.

"The brain is not like any other part of the body. That means operating requires more work from the standpoint of whether removing the tumor will destroy part of the brain's function. With the brain, we have to be more accurate because there's simply no margin for error," he says.

Each year, about 17,000 Americans are diagnosed with brain and spine tumors. The majority of these are cancerous, but those that are not can often be cured. USC/Norris physicians see about 700 patients each year that have tumors of the brain and spine.

"The main point is, this is a difficult problem and you need a program designed specifically to care for and treat these patients and also to develop new treatments for them," Chen says. This is the guiding principle of the new multidisciplinary program.

Improvements in treatment techniques over the last few decades have included better ways to map an individual's brain using stereotactic localization, a tool that keeps the head immobilized and provides physicians with a precise frame of reference to guide surgery.

"We use functional brain testing during operations so we can determine how areas of the brain near the tumor are being used, and, in addition, employ imaging to determine whether a given lesion is a tumor," he says.

Radiation therapy is now much more precise, radiating only the brain tumor, and is better tolerated. According to Michael L.J. Apuzzo, M.D., director of neurosurgery at the USC/Norris Hospital, "Our published experience and that of others indicates that radiosurgery is now the preferred treatment for the majority of brain metastasis and is remarkably effective in this regard as well as an alternative to open surgery for many benign brain tumors."

The Gamma Unit, under the direction of Apuzzo and Zbignew Petrovich, M.D., provides radiosurgery that is precise and safe in its application. The device-housed in the USC University Hospital, located across the street from the USC/Norris-attacks brain tumors and other intracranial disorders with a focused burst of radiation while the patient is awake and under only a local anesthetic. The 20-ton medical device provides surgeons with a non-invasive, state-of-the-art method to treat inoperable cerebral tumors, pituitary tumors and a range of neurological conditions. It is considered one of the most powerful technical advances in the fight against many difficult brain disorders and diseases.

Actually, the Gamma Knife is not really a knife at all. The "cutting" is done by 201 beams of gamma rays emanating from cobalt 60 sources located in a helmet-like structure placed around the patient's head. Through narrow holes in the 400 pound suspended secondary helmet (which looks like a cross between a colander and a beauty salon hair dryer), these beams of radiation are focused precisely on the target. Though the rays pass through many cells, they are too weak to kill any except those in the exact area they pinpoint.

Soon, the Cyberknife, a new generation of advanced radiosurgical tool, will be in place at the USC/Norris Hospital, offering expanded opportunities for cranial, spinal and more general protocols.

"Each of these instruments represents an "operating room" that serves as a venue for the experience, skills and commitment of the individual surgeon and more so for the collective operative team," says Apuzzo, the Edwin M. Todd/Trent H. Wells, Jr. Professor in Neurological Surgery. "Our USC/Norris team is recognized as being unusual in many regards, but principally for experience and contributions to the field."

Chen notes that even though these improved treatments and techniques cannot yet promise a cure, they can at times provide a longer life and, most importantly, a much better quality of life than could otherwise be maintained. "With treatment, we can often ensure that the patient's pain is decreased and that they experience no paralysis, for example," Chen says.

Marc Chamberlain, M.D., clinical professor of neurology and neurosurgery, the newest member of the multidisciplinary team, co-director of the program and former director of the brain tumor program at UC San Diego, says his background in chemotherapy will provide a "complement to existing surgical and radiosurgical therapeutic perspectives."

Medical oncology approaches now include new medicines and chemotherapeutic agents that can be injected directly into the tumor. Chamberlain and Chen have begun a clinical trial of a new product containing a nitrosourea (carmustine) that is dissolved in ethanol. When injected into the tumor, Chamberlain says, "the alcohol carries the drug rapidly through the capillary system that exists in tumors but not in normal brain tissue. So it fills the entire tumor but once it enters normal brain it is quickly metabolized and removed from the brain." USC/Norris is one of only seven sites in the country that will test this drug, he says, and "it has potential. We're excited."

Brain tumors are an often-ignored stepchild of chemotherapy research and development, says Chamberlain, because the number of patients is relatively small; brain cancer makes up only about two percent of all cancers, or about 17,000 cases per year. "That's not much when compared with breast cancer, which has 180,000 new cases a year."

Of the 45 chemotherapy agents in use in the U.S., "about one quarter can be used for brain tumors," says Chamberlain. "Many of the drugs used for brain tumors were not developed for brain tumors specifically. We're still looking for brain-specific chemotherapy agents."

The search is important not only to those with primary brain tumors but for thousands of other cases in which other cancers metastasize to the brain. "Melanoma, for example, often metastasizes to the brain, as does breast cancer. So brain cancer is not an insignificant disease," he says.

There have been a few chemotherapeutic bright spots, he observes, including the recent development of a drug called Temodar that is specifically for brain tumors. "It's become a favorite because it's oral, has few side effects and has well-established efficacy," he notes. "But we still need new therapeutics and new combination therapies."

"Unfortunately," he says, "despite intensive clinical research for the most common brain tumors-like the one that movie critic Gene Siskel suffered-we have not significantly impacted the median survival time of that disease. When you sit with the family and tell them what to expect, it's not significantly different from 30 years ago. That's a bit discouraging."

However, there has been some progress in creating longer survival rates, thanks mostly to improved surgical radiotherapeutic and radiological techniques. Microsurgical techniques and tools, brain mapping, and even robotics mean surgeons can be more targeted and cause less harm. Improved radiotherapy, like the Gamma Knife, means "we can deliver extremely focused radiation to essentially anywhere in the brain," Chamberlain says. "Today, treatment is more sculptured and we can deliver minimal and hopefully nondestructive doses."

Chamberlain hopes that, in the variety of therapeutic options that the new neuro-oncology program will offer at USC/Norris, "we'll be able to make some substantial gains in this field."

Arun Amar, M.D., clinical instructor of neurological surgery, says, "It's not misleading to say that there is hope. Although large studies don't corroborate the effectiveness of many new treatments, there is anecdotal evidence that some patients are doing better. And there's often a lag time between the introduction of new techniques and the time when we gain enough experience with them to make them clinically useful."

He lists several areas of current investigation:

Acknowledging that hard challenges remain in the fight against brain and spinal tumors, Chen says, "the bottom line is these tumors are very resistant to treatment."

Still, he and his colleagues believe progress is being made and they remain optimistic that 30 years from now physicians will be able to provide patients with far more effective treatments, and along with them, hope.