External-beam radiotherapy can rapidly relieve the pain of uncomplicated bone metastases, which makes EBRT one of the most commonly prescribed treatments. Its application, however, has been mired in debate over whether this palliative modality should be administered in single- or multiple-fraction regimens.
A new ASTRO guideline promises to end the handwringing by radiation oncologists who worry about choosing the right regimen. Scheduled for publication this fall in the International Journal of Radiation Oncology, Biology, Physics, the guideline concluded that single- and multiple-fraction regimens are so similar in clinical efficacy that the patient's circumstances and concerns should determine the choice (see Table).
"Over the years there have been discussions about whether one-fraction or multiple-fraction [regimens] are optimal," said Stephen Lutz, MD, director of radiation oncology at Branchard Valley Regional Cancer Center in Findlay, Ohio. "With a couple caveats, [the guideline shows that] either one is reasonable."
Dr. Lutz handpicked and then led the committee of 17 experts in palliative radiotherapy that developed the guideline. This guideline will provide the basis for oncologists to feel comfortable offering either single- or multiple-fraction regimens to their patients.
"When you're talking about people, about their wishes, you can be surprised," he said. "Their choices can be widely variant."
Often the choice comes down to time, efficacy, and how each is perceived by the patient. Because many with metastatic bone disease have only a short time to live, multiple treatment regimens can absorb much of their remaining lives. By definition, single-fraction treatment is quick, relatively convenient, and cost-effective. The downside is that single-fraction therapy is associated with a 20% retreatment rate to the same site vs an 8% retreatment rate after a multiple-fraction regimen.
Multiple-fraction regimens, typically 10 doses totaling up to 30 Gy, have been incorrectly perceived to provide better long-term pain relief than the short course, often an 8 Gy single treatment. This misperception, when coupled with unfounded concerns about higher rates of pathologic fracture, spinal cord compression, and radiation myelitis after single fraction treatment, has limited the widespread use of single-fraction treatment. Complicating matters is the possibility that the patient may feel that "more is better" and that single-fraction treatment must therefore be inferior.
The ASTRO guideline deflates this patient concern, however, by putting the others in context. Research compiled by the committee indicates that the differences between single- and multiple-fraction regimens are minor.
Although a regimen of 30 Gy in 10 fractions has a lower incidence of retreatment of the same painful site, prospective randomized trials demonstrate that single-fraction EBRT provides equivalent pain control with similar or fewer side effects. If pain recurs, a single 8-Gy fraction can be safely and effectively repeated, according to the guideline. An added advantage of single-fraction treatment is its increased efficiency.
The guideline was completed in just eight months. In this time, the ASTRO committee examined data from 25 randomized trials, 20 prospective single-arm studies, and four meta-analyses/systematic reviews. The committee then gathered and incorporated the data into a final draft with comments from the oncology community and ASTRO board.
"The underlying comment we got was that it was imperative that [the guideline] make it clear there are good choices, not just one choice," Dr. Lutz said.
Stereotactic body radiotherapy was found to hold "theoretical" promise as a treatment for new or recurrent spine lesions, though the committee recommended that its use be limited to highly selected patients at centers familiar with the dosing and risks of SBRT and, preferably, on a prospective trial.
With regard to single- or multiple-fraction regimens, the choice depends on the patient and surrounding circumstances, according to Dr. Lutz. The more fractions, the less the chance pain will return and repeat treatments will be needed.
"But for someone who is really very sick and almost certainly approaching the end of life, they are probably much more willing to do a single fraction for the sake of convenience," he said. "Any more than one fraction, when someone is actively dying, is probably overdoing it."