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  HEALTHWIRE I MARCH, 2002 I CONTACT: DONNA M. CARROLL, M.A., M.S. (616) 344 1946
   
  New Therapies Target Brain Tumors
   
 
   
  Brain tumors are among the most difficult of cancers to treat. Hidden within the skull and protected by the blood brain barrier that prevents toxins, including chemotherapy, from reaching delicate brain tissues, the brain is less accessible and less amenable to treatment than other organs.

Improvements in imaging techniques that allow us literally to look inside the brain are allowing earlier detection and diagnosis of tumors. Radical new approaches to treatment as well as refinements in more traditional therapies are lengthening survival time for some brain tumor patients and offer hope for more effective treatment options in the future.
Not all brain tumors are alike. Some are essentially benign and if removed may never return. Others are aggressive and highly malignant and usually return in the months following surgery. Tumors are normally classified according to cell type; rather than referring to them as benign or malignant, physicians generally prefer to talk about them as secondary tumors, which often have a very good prognosis, and malignant primary tumors that tend to have a poor outcome.

Tumors of the brain and spinal cord can occur at any age, and no specific cause has been identified. They are most common in adults over age 50 and in children. Brain and spinal cord tumors are the second most common form of cancer in children, accounting for about one fifth of all childhood cancers. Generally, children with brain tumors fare better than adults.

According to the American Brain Tumor Association, 180,000 people were diagnosed with brain tumors in 2001. Of that number, more than 16,000 were diagnosed with a malignant primary brain tumor, the most serious kind. The most common malignant brain tumors, glioblastoma multiforme and anaplastic astrocytoma have a poor prognosis because they tend to recur despite treatment. A great deal of research is focused on these tumor types in an effort to improve outcomes.

High-Tech Helpers
Sophisticated noninvasive imaging techniques that allow doctors to look inside the brain include PET scans and magnetic resonance imaging (MRI).

An MRI can detect and pinpoint the position of a tumor, providing a three dimensional image of the mass. An accurate picture of the tumor makes it possible to target surgery and follow-up radiation to highly specific areas.

Surgery to remove a brain tumor is the initial standard treatment. Often the surgery can be performed through small holes drilled in the skull. Unfortunately it’s never possible to remove the entire tumor. Surgery to remove a breast lump takes out the lump plus a margin of healthy tissue surrounding the lump to ensure that all the cancerous cells are removed. Taking a margin of healthy brain tissue would destroy healthy brain cells with unacceptable results for the patient. The challenge for the surgeon is to remove as much of the lump as possible while leaving healthy tissue intact. Surgery is then followed by radiation or sometimes chemotherapy to try to eradicate the remaining tumor cells.
A new form of radiation delivery has shown promise in extending the life of some brain tumor patients. The new technique, called GliaSite is currently being tested in clinical trials at Stanford University Medical Center.

Rather than delivering radiation through the scalp and healthy brain tissue, this technique uses a balloon attached to a catheter that is threaded to the site to deliver radiation. It allows more controlled delivery of higher doses of radiation directly to the area from which the tumor was removed.

Traditional surgery and radiation therapy extends the life of patients with invasive tumors by about a year. GliaSite has extended survival to about 80 weeks. A number of other targeted approaches to radiation delivery are being investigated at other medical centers.
Photodynamic Therapy (PDT) offers a different approach to targeting cancerous cells left behind after surgery. Currently in Phase III clinical trials at multiple sites, PDT uses red light at a specific wavelength to destroy tumor cells that have been treated with a photosensitizing agent.

Patients are given a photosensitizing drug (porfimer sodium is the drug most often used) which accumulates in tumor cells. Then a catheter carrying optical fibers is introduced to the site from which the tumor was removed during surgery. A red light generated by a laser is transmitted to the optical fiber, destroying malignant cells in the proximity of the fiber.
The advantage of PDT is that it is relatively selective, killing tumor cells but sparing healthy tissue, and it works regardless of tumor cell type. There is no cumulative tissue damage, and the procedure can be repeated if necessary.

Disadvantages of this approach include swelling in the brain that accompanies the death of tumor cells. The therapy is usually done after surgery, using the cavity left by the tumor removal to allow space for some of the swelling.
Another complication is the light sensitivity patients suffer after receiving the photosensitizing drug. Eyes and skin must be vigilantly protected from natural light for about 30 days. Patients need to wear protective clothing and glasses and to stay out of sunlight for that period.

A number of other photosensitizing drugs are also being tested. More information about clinical trials of PDT can be found at the National Cancer Institute’s Cancernet Website (http:/cnetdb.nci.nih.gov/trialsrch.shtml)

A different solution in being pursued by researchers at Duke University using genetic engineering to modify a poliovirus. The virus has shown early success in treating brain tumors in mice.

Researchers chose the poliovirus because it selectively targets brain cells, making it an excellent delivery system for a virus aimed at brain tumor cells. To avoid the risk of causing polio, the poliovirus has been combined with the rhinovirus, the virus responsible for the common cold.

The engineered virus was tested in mice with experimental brain tumors. The tumors were destroyed within days after a single dose of the virus replicated in the cancerous cells. Researchers now need to test both the safety and effectiveness of this approach in humans, usually a lengthy process.

Research into better ways to treat brain tumors continues on multiple fronts. Better delivery systems for chemotherapy, more targeted approaches to radiation therapy and recent breakthroughs in genetics raise hope for better survival rates and cures. For brain tumor patients, the National Cancer Institute is a valuable source of information about ongoing clinical trials and the most recent treatment options.

REFERENCES:
“Better Treatments for an Enigmatic Disease,” Harvard Health Letter, April 1998.
Edward E. Conway, Jr. et al, “Diagnosing and Managing Brain Tumors: The Pediatrician’s Role,” Contemporary Pediatrics, November 1999.
Charles Eberhart, “Decreasing Incidence of Sudden Death Due to Undiagnosed Primary Central Nervous System Tumors,” JAMA, December 26, 2001.
“Genetically Engineered Poliovirus Fights Brain Tumors,” Cancer Weekly, June 5, 2001.
Edward Laws, Jr. “Central Nervous System Tumors: What Have We Learned and Where Are We Heading?” Ca, November 1998.
Jeannette K. Lowry, “Brain Tumors in the Elderly: Recent Trends in a Minnesota Cohort Study,” JAMA, December 23, 1998.
Troy May, “New Form of Brain-Tumor Radiation Promises to Extend Life,” Silicon Valley/San Jose Business Journal, December 2001.
J. Netting, “Poliovirus Slaughters Brain Tumors in Mice,” Science News, May 26, 2001.
Teresa Tarnowski et al , “Photodynamic Therapy: A Novel Treatment for Primary Brain Malignancy,” Journal of Neuroscience Nursing, December 2001.
“Technique Delivers Brain Tumor Chemotherapy Across Blood-Brain Barrier,” Cancer Weekly, February 22, 2000.

   
 
 
 
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