New Hope fbr Brain Tumor Patients

Primary brain tumors—those that originate in the brain rather than metastasizing from other parts of the body—are among the most virulent of cancers. The most common type, glioma, tends to strike otherwise healthy adults with seeming randomness and is often fatal.* An estimated 17,000 to 20,000 Americans will be diagnosed with a primary brain tumor this year.

Good news: Recent research is giving these patients reason for hope. If you or a loved one has been diagnosed with a brain tumor, here's what you need to know...

TREATMENT ADVANCES

The most aggressive of all gliomas, Glioblastoma multiforme (GBM), is also the most common, with about 10,000 to 12,000 diagnosed in the US annually, most after age 50. The median survival time for someone with GBM is about one year.

These tumors rapidly spread and infiltrate normal parts of the brain, so it's impossible to excise them completely. The traditional approach to treating GBMs has been to surgically remove as much of the tumor as possible and then administer radiation therapy. When the tumor regenerates, as GBMs often do, doctors have prescribed chemotherapy to slow the growth.

Breakthrough: In a recent trial by Canadian and European researchers, GBM patients who were given radiation therapy and the chemotherapy drug temozolomide (Temodar) following surgery did significantly better than those who received radiation alone. A full 26.5% of the patients who received combination therapy were living two years after their diagnoses, versus only 10.4% of the control group. These results were so positive that this approach is now the standard of care for all GBM patients in North America and Europe. More studies are needed to determine its long-term efficacy and safety.

On the horizon: It may soon be possible to identify which GBM tumors will respond optimally to the new protocol. In reviewing their trial dala, Canadian and European researchers noticed that patients whose tumors had an inactivated gene, known as 06-methyl-guanine- DNA methyltransferase (MGMT), did markedly better on the combination therapy than those whose tumors had an active MGMT gene.

*Meningioma, a type of brain tumor that is usually benign, is about twice as common as glioma.

The median survival among patients with inactive MGMT was nearly 22 months, and an astounding 46% of them were alive at two years. Those who had an active MGMT gene survived for a median of nearly 13 months. The gene enables cancer cells to repair themselves after being damaged by certain chemotherapy drugs, rendering the chemotherapy ineffective. We're exploring ways to safely "turn off' the gene in patients for whom it remains active.

OTHER RESEARCH ADVANCES

All cancers are in part genetic, since genes play a role in the development and progression of the disease. Genetic variations also appear to affect whether and to what extent another type of rumor, called an oligodendroglioma, will respond to chemotherapy. This slow-growing tumor is rare and typically occurs in middle-aged adults.

We've long known that an estimated two-thirds of these tumors are sensitive to chemotherapy drugs, while the remaining one-third are largely impervious. Researchers at Massachusetts General Hospital, in collaboration with Canadian colleagues, discovered in 1998 that responsive oligodendrogliomas had one thing in common—loss of parts of chromosomes (cell structures that carry genetic information), specifically chromosomes 1p and 19q. For reasons that are not yet clear, parts of these chromosomes “disappear" in some of these tumors. About 50% of patients with oligodendrogliomas lack these chromosomes. Virtually all oligodendrogliomas lacking both of these chromosomes will have a prolonged response to treatment, while those that retain them, particularly the 1p chromosome, are unlikely to have durable responses to treatment.

While patients with oligodendrogliomas are now routinely screened for loss of 1p and 19q chromosomes, doctors have yet to reach a consensus on how best to treat tumors lacking them. Some still recommend aggressive surgery to remove the bulk of the tumor, followed by radiation and chemotherapy. Others suggest starting with chemotherapy, hoping that patients may be able to avoid surgery and radiation. Both approaches are meeting with success. The median survival rate for these patients now exceeds seven years. Clinical trials are under way to study these treatment approaches.

CLINICAL TRIALS MATTER

All new therapies—surgical, radiological, pharmacological—must prove safe and effective in clinical trials before being prescribed to the general patient population.

One big challenge we face in advancing brain cancer therapies is making patients aware of the clinical trials that may benefit them personally...or lead to lifesaving treatments for future generations. For patients whose brain tumors do not respond to traditional treatment, an investigational therapy may be their best hope.

To learn more about clinical cancer trials, or to find a trial that may be right for you or a loved one, consult the National Cancer Institute, 800-422-6237, www.cancer.gov or the American Cancer Society, 800-227-2345, www.cancer.org.