Science / Medicine : Precision Radiology : Fine-Tuned Gamma Beams Treat Brain Tumors Quickly, Effectively

In cancer treatment, brain tumors often defy doctors’ best conventional therapies.

Chemotherapies seldom work because the natural blood-brain barrier prevents blood-borne toxins (and medicines) from reaching the brain. The use of conventional radiation therapy is limited by the risks of damaging healthy areas of the brain. Surgery, while usually the treatment of choice, may not be possible: Some areas of the brain cannot be safely operated upon.

Now, a new technique may hold hope for as many as 10% of the more than 100,000 Americans diagnosed yearly with brain tumors. They, along with hundreds of others with malformations of brain blood vessels, could benefit from a procedure called stereotactic radiosurgery.

Melding the precision of neurosurgery with the penetration capabilities of radiation, stereotactic radiosurgery aims several precisely focused beams of radiation at the target mass, killing it. Because the dose is concentrated only in the target area, healthy areas of the brain, skull and skin are subjected to only low levels of radiation as the beams pass through them, causing no measurable side effects.

Stereotactic radiosurgery allows neurosurgeons to reach previously inaccessible brain tumors--without opening the patient’s skull. While conventional neurosurgery usually requires a hospital stay of 9 to 12 days, after stereotactic radiosurgery a patient can go home the next day--or in some cases, the same day.

“This is a truly remarkable concept,” said Dr. Michael L. J. Apuzzo, professor of Neurological Surgery at USC School of Medicine, where he began using the technique in 1985.

Agrees USC radiation physicist Dr. Zbignew Petrovitch, “Although the technology and expertise to perform this procedure are extremely complex, the end product produces not only less human suffering but real progress.”

The technique does have limits. It cannot be used to kill tumors in other parts of the body. Because the technique relies on precise aim, the area being treated must be kept completely still. A hatbrim-like frame, attached to the skull with needle-thin screws, immobilizes the head. Organs other than the brain, however, move with every breath, so stereotactic radiosurgery cannot be applied to these areas.

Stereotactic radiosurgery cannot cure a patient whose cancer has spread beyond one site. It is ineffective against tumors over 3.5 centimeters in diameter, or a little bigger than a quarter.

But for small, primary tumors confined to the brain, “we can effect a cure in one day,” said Dr. Jay Loeffler, co- director of the Stereotactic Radiosurgery Program at both Brigham and Women’s Hospital and Children’s Hospital in Boston. “For those patients, it’s a home run,” Loeffler said.

Stereotactic radiosurgery is also very successful at obliterating other difficult-to-reach lesions of the brain, such as malformations of blood vessels. Often these congenital tangles of dilated vessels will leak, causing brain hemorrhage and stroke. Although frequently treatable with microneurosurgery in some areas of the brain, surgeons risk damaging crucial nerves. “Stereotactic radiosurgery opens a whole new arena for treating lesions of the brain,” said Apuzzo.

Although the technique can only be applied to a fraction of the cancer cases in the United States, it solves the single greatest problem in cancer treatment today: protecting healthy tissue while destroying tumor cells. “We could cure every cancer known, if only we had a way of protecting normal tissue,” said Loeffler.

This is why conventional radiation therapy is administered in divided doses over a several-week period, allowing healthy tissue time to recover from the radiation. Unfortunately, tumor cells may eventually grow back, too; brain tumors treated with conventional radiation alone usually recur within 6 months to 2 years, Loeffler said.

Because stereotactic radiosurgery concentrates its effects within the tumor area, in a single session, patients can receive a much higher dose of therapeutic radiation, so that regrowth is a much more remote possibility. Patients are also spared the fatigue, reddened skin and nausea that sometimes accompany conventional radiotherapy.

The concept of stereotactic radiosurgery was developed in the 1950s by Swedish neurosurgeon Lars Leskell. He invented a machine called the gamma knife to deliver multiple, focused beams of gamma radiation, produced by cobalt 60, to the target area. But guided only by two-dimensional images from X-ray films and angiography, doctors at that time could only approximate a mass’s size, shape and position within the three-dimensional space of the skull.

In the 1970s and ‘80s, however, computed tomography (CT) scans and magnetic resonance imaging (MRI) provided new, three-dimensional views of hidden tumors. This advance made stereotactic radiosurgery more than just an interesting concept--doctors could now pinpoint the target of the multiple beams of radiation.

Here is how it works:

Before the actual radiosurgery, a nickel-plated aluminum head ring, or frame, is screwed into the bone of the skull with four needle-thin pins, inserted under local anesthesia.

Next, a localizing unit is attached to the frame. The localizing unit’s nine rods (six vertical, three diagonal) protrude outward from the frame and serve as a three-dimensional reference system, like longitude and latitude on a map, while CT or MRI studies are performed. The tumor pinpointed, next specialists calculate and plot the number, strength and angles of the radiation beams to be fired at the target.

Only a handful of American institutions are using stereotactic radiosurgery, although interest in the technique is high worldwide. In 1987, with gamma units operating in Sweden, England and Argentina, the first American gamma unit opened in Presbyterian University Hospital in Pittsburgh. The next year, the American College of Surgeons featured the unit’s director, Dr. Dade Lunsford, at its annual Clinical Congress. His report: In all 250 patients treated world-wide with the technique, the tumors had stopped growing. In 40% of the cases, the tumors had shrunk.

Gamma knife units are operating in Pittsburgh, Chicago, Atlanta, Dallas, Charlottesville, Va., and Rochester, Minn. The units cost $4 million to $8 million to install, so a procedure typically costs from $10,000 to $20,000, not including physicians’ fees. Because the units’ radiation source is cobalt 60, with a half-life of five years, hospitals must construct a separate building to load each new cobalt core.

To develop a less costly model, specialists at Kenneth Norris Cancer Hospital of USC and Boston’s Brigham and Women’s Hospital began collaborating with overseas investigators in the early 1980s in hopes of making stereotactic radiosurgery more widely available. USC has treated hundreds of people with the technique; Brigham and Children’s hospitals in Boston have treated 240 with the technique since 1985.

“If money was no object, we’d design an apparatus from scratch,” said USC radiation physicist Petrovitch. “But that would cost several million dollars. So we are utilizing an instrument that is already available--the linear accelerator--and modifying it to this particular use.”

Linear accelerators, using X-ray radiation, are standard equipment at major cancer centers. In conventional radiotherapy, the linear accelerator delivers its energy in a broad photon beam. The investigators developed devices to focus the accelerator’s beam. By integrating the machine with imaging and computer equipment, “we were able to develop a treatment method that closely resembled the gamma knife principle but was much simpler, less expensive and potentially accessible to more patients,” Apuzzo said.

Using the linear accelerator, there is only one source of radiation, but it moves. Both the linear accelerator machine and the patient’s couch are rotated to achieve the angles at which the beams are fired to concentrate at the center of the tumor. With this more flexible setup, said Apuzzo, the use of stereotactic radiosurgery could be expanded to treat more brain tumors of different size and contour.

“We’re not looking at an instrument where all the answers are in yet,” said Apuzzo. “In theory, its application is only limited by a lesion’s size and whether it can be localized by imaging. Our expectations are extremely high.”