Brain Tumors: Primary

Description

Alternative Names

Radiotherapy

Radiotherapy plays a central role in the treatment of most brain tumors, whether benign or malignant.

Radiotherapy after Surgery. Even when it appears that the entire tumor has been surgically removed, microscopic cancer cells often remain in the surrounding brain tissue. Radiation targets the residual tumor with the goal of reducing its size or stopping its progression. If the entire tumor cannot be removed safely, postoperative radiotherapy is often recommended. Even some benign gliomas may require radiation, since they may be life-threatening if their growth is not controlled.

Radiotherapy When Surgery Is not Appropriate. Radiotherapy may be used instead of surgery for inaccessible tumors or for tumors that have properties that are particularly responsive to radiotherapy.

Radiotherapy and Chemotherapy (Radiochemotherapy). Combining chemotherapy with radiotherapy is beneficial in some patients with high-grade tumors.

Specific Radiation Treatments

Various radiation treatments are now available.

• Conventional radiotherapy uses external beams aimed directly at the tumor and is usually recommended for large or infiltrating tumors. It begins about a week after surgery and continues five days per week for six weeks. It should be noted that older adults have a more limited response to external-beam radiation therapy than younger people.

For tumors that are highly localized, the radiation therapist has a choice of other radiation treatments:

• Brachytherapy (also called interstitial radiation) uses radioactive "seeds" implanted directly in the tumor site. It is used as a booster to external beam radiation for patients with malignant astrocytoma. Brachytherapy appears to prolong survival in some aggressive gliomas. It may also be a safe and effective treatment for some children.
• Conformal three-dimensional conformal radiation uses high-dose radiation beams shaped to match the shape of the glioma. This technique is highly targeted and, in certain cases, may even be used with some success for patients who have had previous radiotherapy.
• Hyperfractionated radiation uses many small radiation doses to deliver a high total dosage of radiation.
• A balloon catheter (GliaSite) that delivers radiation to the tumor cavity after surgery is showing promise.

Stereotactic Radiosurgery

Stereotactic radiosurgery has been developed to allow highly targeted radiation to be delivered directly to the small tumors while avoiding healthy brain tissue. The term radiosurgery is used because the destruction is so precise that it acts almost like a surgical knife. Some studies are finding that stereotactic radiosurgery improves survival, even in patients with the highly aggressive glioblastoma multiforme brain cancer. The procedure is being tested to boost standard radiotherapy.

Benefits of Stereotaxy. There are a number of benefits for stereotaxy:

• Stereotaxy allows precisely focused, high dose beams to be delivered to gliomas less than 1.25 inch in diameter.
• Investigators have found that stereotactic radiosurgery can help them reach small tumors located deep in the brain that were previously considered inoperable.
• Sometimes with stereotaxy only a single treatment may be needed.
• Unlike traditional radiotherapy, stereotactic radiotherapy can be repeated, so it is useful for recurrent tumors when a patient has already received standard radiation treatments.
• Combining stereotaxy with techniques that gauge speech and other mental functions in patients who are awake during the procedure can allow removal of brain tissue with a lower risk for complications in areas that affect such functioning.

The Planning Procedure. Stereotactic radiosurgery usually begins with a series of steps designed to plan the radiation target:

• First, the patient is given a local anesthetic. In the standard operation, the patient's head must be totally immobilized by screwing a device known as a stereotactic frame into the patient's skull. (The frame procedure is effective only on brain tumors that have regular margins.) The frame is removed as soon as the whole procedure has been completed (about three to four hours.)
• A three-dimensional map, usually using magnetic resonance imaging scans (MRI), is made of the patient's brain.
• A computer program calculates dosage levels and specific areas for radiation targeting.

Advanced imaging techniques are now allowing frameless stereotaxy, which eliminates the frame and may be effective on more tumors. For example, high-field interventional MR imaging (iMRI) uses a guidance system based on cruise-missile technology to calculate the slightest variations in movements of the head and the location of the tumor relative to these movements. These calculations are then used to target the radiation beams directly on the tumor, even if the patients head is moving slightly.

Delivery of Radiation Beams. Once the preliminary planning stage has been completed, treatment begins. A number of advanced machines, such as the gamma knife, adapted linear accelerator (LINAC), and cyclotron, are being used with stereotaxy and can deliver very focused beams of radiation. Actual treatment takes 10 minutes to an hour.

• The gamma knife uses gamma rays that are sent from multiple points to converge at a single point on the tumor. Although each gamma-ray beam is very low dosage, when the beams converge, the intensity and destructive power is very high. The gamma knife is limited to very small tumors and so is generally useful as booster after standard radiation, surgery, chemotherapy, or combinations.
• The linear accelerator (LINAC) produces photons (positively-charged atomic particles) in patterns that are matched to the tumor shape. The patient is positioned on a bed that can be moved to allow flexible positioning. It allows treatment over multiple sessions of small doses (fractionated stereotactic radiotherapy), instead of a single session. This means that larger tumors can be treated.
• The cyclotron is basically an atom smasher, which produces protons that can be directed toward the tumor. As part of this procedure, some researchers are using boron neutron capture therapy (BNCT). BNCT employs intravenous administration of a boron compound, which is picked up more selectively by tumor cells than by normal brain tissue. The cyclotron delivers a single dose of radiation that triggers the release of high-energy particles from the boron that destroy nearby tumor cells. The cyclotron is available only in a very few locations and there have been few trials to date.

Drugs Used With Radiation

A number of drugs may be used along with radiation that may increase the effectiveness of the treatment:

Radioprotectors. They protect healthy cells during radiation

Radiosensitizers. These agents make cancerous cells more sensitive to radiation. For example, combinations of the radiosensitive drugs iododeoxyuridine, 5-FU, and hydroxyurea are promising. Such treatments usually require aggressive use of other protective agents to prevent severe side effects.

Radioenhancers. These drugs, such as topotecan, increase the effects of radiation. Topotecan combined with other drugs, such as thiotepa and carboplatin, may help children with neuroblastoma and brain tumors. A 2002 study using topotecan for glioblastoma multiforme was disappointing, but different methods of administration or other similar drugs may be useful. Efaproxiral, an investigative agent that increases oxygen in the brain, is showing promise as a radioenhancer.

Side Effects of Radiation

Common Side Effects. Side effects of radiotherapy include hair loss, nausea and vomiting, and fatigue. In some cases, radiation may worsen some existing symptoms of brain tumors, seizures, difficulty in swallowing, and movement problems. Fluid build-up (edema) may occur. Such side effects are usually temporary and treatable with steroids. Patients often develop problems in thinking and concentration after radiation treatments. One study suggested that administering oxygen under pressure, called hyperbaric oxygen, may provide some small benefits. It is sometimes difficult to tell symptoms of the disease from those of the treatments.

Tissue Injury. Radiation necrosis (total destruction of nearby healthy tissue) occurs in about 25% of patients treated with radiation. This condition is highly associated with reduction in mental functions. In nearly half the cases of standard radiation therapy, additional surgeries are needed on areas injured by radiation. Other treatments that are showing promise for treating necrotic tissue include administration of oxygen and pentoxifylline (an agent that improves blood flow).

Secondary Tumors. Of concern is a study reporting a few cases of second tumors developing in the areas treated with radiosurgery. The incidence appears to be very low, but experts suggest continued surveillance may be appropriate.

Specific Issues in Radiation Therapy for Small Children. In small children, radiation therapy can impair growth and learning. Precise radiation techniques, such as three-dimensional conformal radiation therapy, may help some children while limiting the injury to healthy brain tissue. Growth hormone is often used after radiotherapy and is effective in restoring growth in many of these children. Although there has been some concern that growth hormone may increase the risk of relapse, a 2000 study reported that, in fact, these children had a lower rate of recurrence than those who did not take growth hormone.