Question: What are the recent advances for brain tumors?

Answer: There are many different types of brain tumors ranging from small, benign tumors that require no treatment to malignant, aggressive tumors that need a wide array of aggressive and sometimes experimental therapies.

Improved brain tumor management begins with diagnosis. Advances in the field of neuro-imaging have led to better methods for visualizing the anatomy and physical characteristics of brain tumors. CT (computed tomography) and MRI (magnetic resonance imaging) scanning of the brain revolutionized the diagnosis and treatment of brain tumors in the 1970s and 1980s. Recent techniques in MRI spectroscopy, which reveals the physiology of treated brain tumors, can differentiate an actively growing tumor from dead tissue. Functional MRI can map the brain function surrounding a tumor, which can help in designing surgical approaches to remove a tumor while avoiding brain damage to areas critical for normal functioning.

Another major diagnostic advance has been in better characterizing the genetic makeup of brain tumor cells. As researchers look more critically at the chromosomes and genes of brain tumors, they are finding a number of different genetic or molecular characteristics that can help guide treatment. For example, we now know that patients with oligodendroglioma who have a loss of genetic material in two specific chromosomes (1p and 19q) have significantly higher response rates and longer periods of survival than patients who lack these genetic changes. Further studies of gene expression in brain tumors will hopefully result in the development of drugs specifically targeted to either stop growth or kill brain tumor cells.

Progress has also been made in treating brain tumors with new and improved methods of surgery, radiation and chemotherapy, as well as our ability to combine various treatments. The most difficult tumors to treat are primary malignant brain tumors. Used alone, surgery, radiation and chemotherapy are unable to successfully treat these tumors. Yet, we are beginning to combine these modalities in new combinations to have a favorable impact on patient survival.

One example of combining therapeutic modalities is the development of convection-enhanced delivery of anti-tumor drugs in patients with glioblastoma multiforme (GBM). The agent is directly infused into the brain to bypass the blood-brain barrier. An ongoing international phase III study, known as the PRECISE trial (www.precisetrial.com), is investigating the effectiveness of this technique with an agent called IL13-PE38QQR, a bacterial toxin derivative paired with a tumor-targeted protein called interleukin 13 (IL13). The drug is delivered through two to four small catheters implanted in the area of the brain where the tumor was removed. The drug is slowly pumped into the brain tissue where it attaches to the IL13 receptor on remaining tumor cells and promotes cell death. The new method is also being tested before surgery to shrink the tumor.

Already approved for use by the Food and Drug Administration is the widely used oral agent Temodar® (temozolomide), a drug that crosses the blood-brain barrier. For the first time in many years a significant improvement has been observed in the outcome of patients with GBM using the drug in combination with surgery and radiation. Temodar is generally well tolerated.

Direct delivery of chemotherapy to the tumor can be achieved by neurosurgeons placing disc-shaped drug wafers called Gliadel® Wafers in the cavity created during removal of the tumor. The FDA approved the wafer in 2003 for use at the time of initial surgery for newly diagnosed high-grade malignant glioma patients.
Advances in radiation delivery have also made it possible to deliver treatment more effectively and safely. New ways of focusing radiation beams, such as Gamma Knife® technology, have allowed us to deliver more radiation to the tumor and less to the surrounding normal brain tissue. With Gamma Knife, an MRI and/or CT provide high-resolution images that aid physicians in plotting delivery of high-intensity radiation beams to the tumor.

There are also new computerized robotic radiation delivery systems available, including CyberKnife®. The guidance technology tracks the position of the tumor using the patient’s skeleton as a frame of reference. Images taken during the procedure are correlated with preoperative imaging scans and these data direct a robotic arm, which moves around the patient, focusing the beams on the tumor.

Bringing these important advances together for successful treatment of brain tumors requires a dedicated medical team working together with the patient and his or her family.

—Jeffrey Cozzens, MD, Neuro-Oncology Neurosurgery, Evanston Hospital, Illinois & Associate Professor of Neurosurgery, Northwestern University