Stereotactic Radiosurgery: No Longer Just a Backup
Stereotactic Radiosurgery: No Longer Just a Backup
Indiana researchers finding new hope for inoperable patients
By Julie Crawshaw
Stereotactic radiosurgery, which was once used only as a backup modality to radiation therapy for patients with brain cancer, appears to be coming into its own in a clinical trial at the Indiana University School of Medicine at Indianapolis. Mark D. Williams, MD, FCCP, director of the Pulmonary Oncology Department, is one of the trial’s two principal researchers. Williams says this research protocol began in February, and nine pulmonology patients have gone through the first phase thus far. "This is a very rigorous research protocol," Williams says. "We are currently testing three patients at each level of radiation." All subjects have medically inoperable stage one lung cancer.
Williams and co-principal researcher Robert D. Timmerman, MD, started subjects with three treatments of 800 rads, advancing to 1000, 1200, and to the current 1400 as patients evidenced their tolerance. The study is currently at 1400 rads. The dosage will continue to increase until it becomes toxic to the patient, at which point the researchers will know how far they can go. "It’s our opinion that we’re going to get to a much higher level of radiation than with standard radiation therapy," Williams says.
Stereotactic radiation is a "lung-sparing" technique, one that can treat deep-seated lung tumors without injuring the surrounding tissue, much like removing a peach pit without bruising the flesh of the fruit. Williams says that it’s too early to tell if the treatment has affected the subjects’ survival rates, but thus far there has been no toxicity from the dosage, which is the focus of the phase one study. The team plans to look at one-year, two-year, and three-year survival rates.
The youngest patient in the study is 54 and the oldest is 86. "He’s a spry 86," says Williams. "He’s tolerating the treatment very well." Some tumors have shrunk significantly, some have almost disappeared, and no one has had side effects. Once they ascertain the highest, safest dose subjects can handle, Williams and Timmerman will begin phase two of the study with another 30-35 patients.
The stereotactic process is different from standard radiation therapy. Standard external beam radiations use multiple beams front to back, all in the same direction. The Indiana researchers’ stereotactic equipment uses up to seven different beams coming from seven different directions to converge upon the tumor. "That allows us to target the radiation much more accurately," says Williams. "Therefore, we can spare the noncancerous lung. We use some very advanced 3D computer software to calculate the size and angles of the dose." A computerized tomography (CT) scan is done while the patient lies in the frame. The 3D software calculates the shape of the dose, determining how it’s delivered. The technology uses an image that’s registered stereotactically, meaning that every image can be realigned appropriately in three-dimensional space; therefore, a therapy based on those images can be guided with a high degree of precision. Feducial markers in the study are well known and clearly registered.
Timmerman says that he became interested in technology being developed in Sweden in 1997. "They were treating patients with metastases, people with incurable problems who needed treatment at local sites in the liver, lung etc." The Swedes had been using this therapy since 1992, using very high doses of radiation in a few fractions rather than the typical radiation treatments of many fractions given over many weeks. "It was more akin to the experience of stereotactic radiosurgery using a gamma knife, which was also developed in Sweden, both in terms of how it’s given and the high radiation dosage levels," Timmerman says.
Karolinska Hospital in Sweden developed the body frame box, which contains the feducials that appear on CT and magnetic resonance imaging (MRI) scans. The box has an immobilization device that hugs the patient with a vacuum pillow, which then conforms to body shape so that the patient can be placed in exactly the same position for every treatment. The third aspect of positioning the patient is a device that presses on the abdomen. "The abdominal compression decreases respiratory motion and, therefore, decreases the motion of the tumor and allows us to shrink our margins, which are only 5 mL to 1 cm around the target as compared to margins of 2-5 cm in conventional radiation therapy," says Timmerman. "It’s a rifle bullet instead of a shotgun." Indiana University acquired the stereotactic technology through the Indiana Lions Club, which raised more than $70,000 to buy the equipment, a nickel at a time, putting on pancake breakfasts.
For several years, Williams and Timmerman treated patients with incurable cancers and metastases from colon cancer, sarcomas, breast cancers, and lung cancers. They were aiming at palliating the first patients but found that when they treated a lesion there was usually a high rate of success. "Another tumor might pop up later on," Timmerman says. "But in terms of what we aimed at, the treatment was 80-90% effective."
Now, they are specifically treating patients with early stage lung cancers that have not spread beyond the site where the tumor began. "This is the first population we’re studying to whom this might make a big impact on survival rates," Timmerman says. "If this is the only thing they have, and they control it with high probability, we could cure them, and this is different than what we’ve done before."
Rather than treat these patients ad hoc, the two decided to write a protocol to formally study this therapy. The first phase focuses on what dose to give, because the Swedes were giving high doses without actually having studied how they picked those doses. Once Timmerman and Williams find the maximum dose they can give without toxicity, they plan to study it further in a larger group of patients to determine how efficacious this treatment is. "We think that, based on the success in treating metastases, the response rates will be high. Because this is a very focused therapy, we don’t know what the rates will be elsewhere," Timmerman says. He points out that while surgery does fairly well for early stage lung cancer, the cure rate for the alternative of fractionated radiation without surgery drops from about 50-70% to about 20%. "If this treatment can get even halfway in the middle of that gap, that would have a big impact," he says.
Timmerman emphasizes that the study’s formality is very important. "I think that with new technology, you really have to be careful. When patients are reported in series, they’re selected a certain way, and if you’re not clear as to how they are selected and if all patients are reported or not, the results may not mean anything." Everyone enrolled in this protocol will have similar characteristics, and the research team will follow every patient, whether they do well or poorly. "It’s a formal study done in a population that needs a better treatment," Timmerman says. "When we finally get the results out, the medical community will have more reason to believe them, and therefore use them."
Timmerman says that if the stereotactic radiosurgery works, the protocol will have made a proof of principle for a treatment that can be effective in an incredibly frail patient population. "These patients have many medical problems, problems with breathing, heart, diabetes," he says. "If it works well in this model, we have a reason to translate it to other patient populations, and if they are healthier, they should tolerate it even better."
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