By Kim Dalton

In March 2001‚ Lil Trimboli felt a small lump floating beneath the skin on her chest. Her physician told her he thought it was probably just a cyst‚ but a biopsy revealed melanoma. “Then I knew I was in trouble‚” Trimboli says.

Back in 1985‚ when she had surgery for a rare melanoma of the eye at the age of 26‚ Trimboli says she was pretty naïve about the potential for recurrence. In fact‚ statistically‚ she turned out to be very lucky. For about 15 years she went on with her life undisturbed by the disease‚ following her husband‚ Scott‚ on U.S. Air Force assignments around the world and raising three children. When Scott retired two years ago‚ they settled in a town west of Colorado Springs‚ Colorado‚ both enjoying a vigorous outdoor life‚ including Lil Trimboli’s dedication to distance running.

Now‚ scans showed eight tumors in her liver and a large mass in her ovary‚ all metastases—or new tumors—from the original melanoma. Her oncologist pronounced her situation “very grim” and told her to get her affairs in order. But consultation with a melanoma specialist and research on the Internet led her to a phase I clinical trial of an immune–boosting drug.

After eight weeks of the experimental therapy‚ the cancer in her liver was stable‚ but the mass in the ovary was progressing‚ so it was removed surgically.
Bothered that most of her body was being imaged regularly but not her head‚ Trimboli asked for a brain scan. It showed a 6–millimeter tumor. Rather than surgery or radiation to the entire brain‚ Trimboli chose radiosurgery‚ which focuses high–intensity radiation on the tumor‚ destroying the destructive cells. The strategy was to deal with the brain metastasis quickly‚ so Trimboli could return to her ongoing immune therapy.

The best–known radiosurgical tool is the Leksell Gamma Knife® (the registered trademark of equipment made by Elekta)‚ which earned its moniker for its scalpel–like precision as well as for its dramatic ability to eradicate malformed or diseased tissue with a single high dose of radiation. The Trimbolis made an appointment at the San Diego Gamma Knife Center.

What Is the Gamma Knife?
The Gamma Knife is‚ of course‚ only metaphorically a knife; it doesn’t cut through the skull or brain tissue. The name is misleading in another sense as well. Rather than a knife‚ it’s actually a massive therapy instrument that encompasses a radiation unit with a heavily shielded hemisphere containing sources of radioactive cobalt–60‚ a treatment–planning computer‚ a movable patient couch‚ and headgear.

The key to its success is the ability to locate the coordinates of a tumor in three–dimensional space with sophisticated imaging and then‚ by means of a head–stabilizing helmet dotted with adjustable apertures‚ focus 201 beams of high–intensity radiation within a small‚ well–defined volume. Because each individual beam is relatively low energy and very narrow‚ passing through only a tiny corridor of brain en route to its target‚ it leaves most normal tissue unharmed.

Unlike conventional surgery‚ radiosurgery doesn’t remove a mass; rather‚ it kills individual malignant cells over weeks and months by damaging DNA‚ which interferes with cells’ ability to reproduce.

Unsheathing the “Invisible Blade”
The process for Trimboli once in San Diego was to leave early in the morning for the Gamma Knife center. After an I.V. was started for any needed medications‚ a local anesthetic was administered to numb the skull where the headgear would be attached.

“That was the worst part‚” says Trimboli. “I could hear the screws grinding on bone.”

She also found it uncomfortable being locked into the MRI by the head frame. (Keeping the head immobilized is important to ensure the accuracy of the targeting.) Data from the MRI fed into the system’s computer program plotted the attack.

After the imaging‚ Trimboli was allowed to get up‚ go to the bathroom‚ and walk around for an hour or two while the operation was being planned. When the medical team‚ including a neurosurgeon‚ a radiation oncologist‚ and a medical physicist‚ was ready‚ she climbed onto a cushioned table‚ which was then moved into the radiation unit.

“The actual zapping was anticlimactic‚” says Trimboli. “It’s very quiet in the machine.” Throughout‚ she was in contact with the doctors via a video monitor and an intercom.

Afterward‚ her face swelled a little‚ and she had a headache from the helmet for a couple of hours. A testament to radiosurgery’s noninvasiveness—and for Trimboli the high point of her trip to San Diego—was the following morning when she was able to run seven miles on the beach. There were no lingering side effects‚ she reports‚ and within a month the tumor had vanished.

When Radiosurgery Is Used
Along with surgery and sometimes chemotherapy‚ radiation—in its conventional form—has long played a prominent role in the treatment of brain cancer. It may be used after an operation to try to kill stray cancer cells that surgery missed‚ or it may be used instead of surgery if the tumor is inoperable because it lies too close to critical areas.

Neurosurgeons have worked toward guidelines‚ still evolving‚ about when it should be used and who is most likely to benefit.

In general‚ the repertoire of brain cancers treatable with radiosurgery includes most malignant brain tumors. With many aggressive brain cancers‚ often the goal is not to cure or even to extend life‚ but to control symptoms and keep the patient comfortable. Consider glioblastoma multiforme‚ a tumor that progresses rapidly. According to one study‚ with surgery alone‚ patients can expect to live about six months; adding conventional radiation therapy extends the prognosis by only three months. Can radiosurgery‚ with its single large dose‚ delay progression and maintain quality of life?

Hesitation about its usefulness stems from the fact that this type of tumor tends to infiltrate surrounding normal tissue‚ making it a more elusive and‚ consequently‚ a less safe target. Two small studies of people with recurrent glioblastoma have shown that radiosurgery can delay return of the tumors by about four months. Another study from the Cleveland Clinic Foundation in Ohio‚ showed patients survived an average of more than 10 months after the treatment. Nonetheless‚ as yet‚ no conclusive data exist that suggest that such patients actually live longer than patients treated conventionally with whole–brain radiation. But there are data that suggest that metastatic disease from generally unresponsive tumors such as melanoma and kidney are more likely to respond to radiosurgery.

Metastatic Brain Tumors
Indeed‚ this single–shot therapy has proven especially suitable for metastatic brain tumors‚ those that spring up from other primary cancer sites. Metastatic brain tumors far outnumber all other brain malignancies‚ affecting about 200‚000 people a year. Most come from melanoma or cancers of the breast‚ lung‚ prostate‚ colon‚ kidney‚ and bladder. Although these patients most often die due to progression of their systemic disease‚ anywhere from 25–50% succumb to complications stemming from their brain metastases.

In general‚ metastatic tumors make ideal targets for radiosurgery‚ since they tend to be more spherical and have cleaner borders. Another consideration: Radiosurgery’s noninvasive strike permits doctors and patients to quickly refocus on fighting the cancer elsewhere in the body.

Radiosurgery’s main strength‚ however‚ is that 85–90% of the time it stops metastatic brain tumors in their tracks‚ says Douglas Kondziolka‚ MD‚ professor of Neurological Surgery and Radiation Oncology‚ the University of Pittsburgh. Halting progression not only removes the immediate mortal danger from such tumors but also keeps them from pressing on critical structures or nerves and causing debilitating symptoms such as headaches‚ loss of motor skills‚ or impaired thinking. In addition‚ brain metastases seem to respond to radiosurgery’s high–intensity beams regardless of where the cancer originated‚ including some types that are characteristically resistant to radiation‚ such as kidney cancer and melanoma.

To be considered for radiosurgery‚ patients must meet certain criteria. Their tumors must be no more than 3.5 centimeters (1.4 inches‚ or about the size of a golf ball) in average diameter‚ says Dr. Kondziolka.

Generally‚ if the tumor is any larger‚ the radiation dose would have to be decreased to avoid complications‚ rendering its therapeutic effect questionable. And radiosurgeons don’t like to treat people with more than four or five brain metastases. But Dr. Kondziolka says the number is variable‚ depending on the patient’s functional status—how independent he or she is—as well as the status of the cancer elsewhere in the body—how well it’s responding to therapy.

“If someone is bedridden‚ they may not be a candidate even if they have only one tumor. But if you’re walking around and feeling good despite having a tumor in your lung‚ even if you have six brain tumors‚ we’d probably operate on you‚” he explains. Of course‚ he adds‚ a tumor that’s pressing on vital structures or causing symptoms calls for conventional surgery.

A Kinder Surgery
Not all patients can tolerate traditional surgery‚ but since there’s no incision with radiosurgery‚ there’s also no risk of bleeding‚ infection‚ or other possible complications of surgery. And for adults‚ it sidesteps the need for general anesthesia with its attendant risks. There is no pain‚ and because it’s usually an outpatient procedure‚ there’s no need for recovery‚ convalescence‚ or rehabilitation.

Another plus for the patient with several metastatic tumors is that they can be dealt with in one session. Unlike conventional radiation therapy‚ it’s over in five or six hours‚ and patients don’t experience nausea or hair loss (except perhaps in small spots if the tumor lies near the skull). More important‚ if new tumors should arise later‚ the Gamma Knife can be called upon again—several times‚ if necessary—where repeated open–skull surgeries would be risky.

Dr. Kondziolka cites a patient of his with brain metastases who nine years ago was given six months to live. He was initially treated with radiosurgery plus whole–brain radiotherapy‚ Dr. Kondziolka says‚ and he has undergone four more Gamma Knife procedures since then. The man has never suffered a recurrence of his original cancer‚ says Dr. Kondziolka‚ “but every few years he keeps getting a couple of new brain tumors‚ and we treat them when they’re small.”

The cost of radiosurgery is substantial—so is the total bill for conventional surgery‚ hospitalization‚ medicine‚ and rehabilitation—but the procedure is covered by most private insurance and Medicare.

Dr. Kondziolka calls the Gamma Knife “a superb device.” But‚ he emphasizes‚ a machine is just a machine—it’s how it’s used that counts. That’s where the radiosurgeon’s training‚ experience‚ and judgment come into play when selecting patients and choosing the right shape and amount of radiation.

“There’s no cookbook for this‚” he says. When choosing a facility‚ consider both the skill of the radiosurgeon and the type of equipment.

Has Radiosurgery Lived Up to Its Promise?
The Gamma Knife does have its skeptics‚ among them Eli Glatstein‚ MD‚ professor of radiation oncology‚ the Hospital of the University of Pennsylvania‚ Philadelphia. He calls the extrapolation of one–shot treatment “problematic” from its initial success in treating problems such as malformed arteries in the brain (where it’s simply a matter of halting a process) to stopping malignant tumors where one has to sterilize billions of cells completely. Allowing just a few aggressive cells to escape can lead to failure. In his opinion‚ the evidence that radiosurgery actually prolongs survival is weak. Moreover‚ he emphasizes that giving a single large dose flouts one of the guiding principles of radiation therapy: exploitation of the difference between cancer cells and normal cells in their response to divided‚ or fractionated‚ radiation doses.

With fractionated radiation doses‚ normal cells are better able to repair any damage they’ve suffered‚ whereas cancer cells‚ a portion of which are always replicating‚ cannot. Over time‚ those cancer cells die in greater numbers. Moreover‚ he observes‚ radiosurgery is at the mercy of the limitations of imaging‚ which can locate a cancerous mass but cannot define its precise borders‚ and thus some of the fingerlike extensions of cancer are bound to be missed by highly focused radiation. Dr. Glatstein says that if in fact radiosurgery is only palliative‚ it represents an extravagant use of scarce healthcare resources to achieve a goal that could be reached far less expensively by medication.

Back to San Diego
The fact that radiosurgery can be repeated proved fortunate for Trimboli because in November 2001‚ her regular brain scan turned up another tumor‚ this time 10 millimeters in diameter. It was back to San Diego for another appointment with the Gamma Knife. This time she knew what to expect. She asked for a sedative for the frame–fixing‚ and her husband later told her she was cracking jokes the whole time. And this time her face didn’t swell.

Trimboli is now on an imaging schedule of every three months. She is continuing with immunotherapy‚ which she has learned to inject herself. The doctors tell her she is NED—no evidence of disease—which Trimboli thinks is “just awesome.” But‚ she adds from experience‚ “It’s important to stay on top of the follow–ups.”