As the world waits hopefully for a miracle that can eradicate brain tumors, tremendous progress is coming from an unexpected direction. Technological advances have led to dramatic improvements in radiation therapy-improvements that have already made a difference in the lives of many brain tumor survivors.

Radiation therapy-the treatment of disease with high-energy X-ray beams-has long been a primary weapon in the war on cancer. It is used today in more than half of all cancer treatments, either alone or in combination with other treatment modalities. It injures or destroys cells in the area being treated (the "target tissue") by damaging their genetic material. Healthy cells can repair themselves to a degree and continue to reproduce themselves, if the dose received is not too high. Cancer cells, however, often have faulty repair mechanisms and lose the ability to reproduce normally. Repeated exposure to high-energy X rays eventually impairs or kills the cancer cells - a desirable goal in treating tumors.

Enough Was Too Much
For years, radiation oncologists faced a frustrating challenge. They knew that by delivering a high-enough dose of radiation to a localized brain tumor, they stood a very good chance of eradicating the tumor and possibly curing the patient. On the other hand, such doses could pose a risk to the normal brain tissue surrounding the tumor. This conundrum has required that some patients be treated with less radiation than ideal for local tumor control and has made it difficult, if not impossible, to optimally treat some tumors.

However, recent advances in radiotherapy are changing the equation. Intensity modulated radiation therapy, or IMRT, is a new technique that enables physicians to deliver greater amounts of radiation to the precise location of a tumor while minimizing the dose to the surrounding healthy tissues. IMRT accomplishes this by carefully shaping the radiation beam so that it conforms to the three-dimensional shape of the tumor, while also allowing the intensity of each radiation beam to be varied or "modulated."

Modulating the Dose
IMRT uses computer-generated images to plan and deliver more tightly-focused radiation beams than are possible with conventional radiotherapy. In addition, with IMRT radiation oncologists acquired the ability to divide the treatment area into hundreds of tiny segments-as small as 2.5 mm by 5 mm. They can deliver a different dose to each segment, hence the term "intensity modulation." Consequently, the dose can be higher in the most aggressive areas of the tumor and lower in areas where the beam is near or passing through healthy tissue. This results in better coverage of the tumor, and greater sparing of the surrounding healthy brain tissues.

Technological Advances
Three major technological developments over the last fifteen years paved the way for IMRT:

1. the digital linear accelerator which generates high-energy X rays and delivers them very accurately,
2. the computer-controlled multileaf collimator - a beam-shaping device with up to 120 computer-controlled mechanical "leaves" or "fingers" that control the shape, size, and timing of the radiation beam, and
3. sophisticated treatment planning software programs that use complex algorithms to optimize a treatment strategy based on each patient's unique diagnostic images.

The Linear Accelerator
The first of these advances is the linear accelerator - a very large piece of equipment that generates the radiation beams used in radiotherapy treatment for cancer. This machine stands approximately nine feet tall by nearly 15 feet long and weighs as much as 18,700 pounds. It rotates around the patient to deliver radiation from nearly any angle. Linear accelerators use microwave energy, similar to that used in satellite television transmission, to "accelerate" electrons to nearly the speed of light (186,000 miles per second). As the electrons reach maximum speed, they collide with a metal target releasing photons, or X-rays. That energy release is measured in millions of volts (MV).

The Multileaf Collimator
The second of these advances is the multileaf collimator (MLC), consisting of a computer-controlled array of up to 120 parallel, and individually adjustable, tungsten slats or leaves that can block the path of an x-ray beam. The MLC is attached to the head of the linear accelerator. The leaves of the MLC are used to create an adjustable opening through which radiation beams are directed at a patient's tumor. The shape of the MLC opening is adjusted to match the shape of the tumor as seen from the angle from which the beam is being delivered. By using the MLC to target precisely shaped beams from several angles, it is possible to deliver a radiation dose that closely matches the 3-D volume of the tumor.

Treatment Planning Software
IMRT uses complex treatment planning software that compares thousands of treatment plan options and calculates the optimal one for each patient. This technique delivers a specified dose of radiation to the tumor while blocking the radiation to surrounding normal brain. IMRT uses "inverse" treatment planning: physicians state their objectives in terms of dose, and the "inverse" treatment planning software "works backwards" from the desired result to create an optimal delivery plan.

Outcomes
IMRT has excellent potential for the treatment of brain tumors, particularly in children. It makes it possible to increase the dose of radiation to a tumor while keeping side effects to a minimum. Children with posterior fossa tumors, for example, currently may experience deafness as a side effect of conventional radiotherapy. Treating certain pediatric brain tumors with IMRT will help to lower the risk of deafness and other serious side effects.

Researchers are actively studying many cancers where IMRT can be effective, including head and neck tumors, prostate and gastrointestinal tumors, lung cancer, central nervous system tumors, breast cancer, gynecological cancer, and sarcoma. The accumulating literature indicates that IMRT planning is not only better than conventional techniques, but IMRT is associated with less treatment toxicity.

This article was provided to us by Patrick Swift, MD, medical director for radiation oncology at the Alta Bates Comprehensive Cancer Center in Berkeley, CA.