Study Finds Fractionated Radiosurgery Reduces Recurrence After Surgery for Brain Metastases, May Improve Survival

Mayo Clinic researchers led a multicenter study that found dividing radiation into several treatments, known as fractionated stereotactic radiosurgery, reduced the risk of cancer returning after surgery for brain metastases and was associated with improved survival compared with delivering radiation in a single treatment.

The findings are being presented today at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting in Boston.

Brain metastases, also called metastatic brain tumors, are cancerous tumors that spread to the brain from elsewhere in the body. Radiation therapy is a standard treatment after surgery, but researchers note that about 30% to 40% of patients experience cancer recurrence at the surgical site despite treatment with single fraction radiosurgery.

"The study findings give us the evidence necessary to transform clinical practice. We can now offer patients a treatment that controls their disease and is associated with improved survival," says Paul D. Brown, M.D., radiation oncologist at Mayo Clinic Comprehensive Cancer Center and co-principal investigator of the study.

Why Dividing Radiation May Improve Outcomes

Stereotactic radiosurgery uses 3D imaging to precisely deliver high doses of radiation while limiting exposure to surrounding healthy tissue. It is typically delivered in a single treatment and is commonly used to treat brain metastases.

"We see high recurrence rates in patients with brain metastases because the challenge is eliminating microscopic cancer cells left behind after surgery without exposing too much healthy brain tissue to high doses of radiation," says Dr. Brown.

Dividing radiation into multiple treatments allows clinicians to deliver a higher total dose. It also gives healthy tissue time to recover between treatments, while tumor cells do not have the same ability to repair.

Previous retrospective studies have suggested that fractionated stereotactic radiosurgery is effective, but the approach had not been validated in a randomized clinical trial.

How Researchers Studied Fractionated Radiosurgery

The study enrolled 242 patients with one to four brain metastases. Each patient had at least one metastasis larger than 2 centimeters that had been surgically removed.

Patients were randomly assigned to receive either a single treatment of stereotactic radiosurgery or fractionated stereotactic radiosurgery delivered in three or five treatments. Radiation doses were based on the size of the treatment area. Brain metastases that had not been surgically removed were treated according to the same assigned schedule.

Researchers followed patients for a median of four years.

One year after treatment, 87% of patients who received fractionated stereotactic radiosurgery had no recurrence at the surgical site, compared with 81% of patients who received a single treatment. Fractionated radiosurgery also better controlled brain metastases that had not been surgically removed, although this result was not statistically significant.

Median overall survival was 29 months for patients who received fractionated stereotactic radiosurgery, compared with 20 months for patients who received a single treatment. Fractionated treatment was associated with a 31% lower risk of death.

"The survival benefit was an unexpected finding, and while the exact mechanism remains unclear, we suspect that advances in systemic therapies over the past decade may be interacting with better control of disease within the brain, and overall, better outcomes for patients," says Dr. Brown.

Researchers found no difference in side effects or complications between the two treatment approaches.

"This is a practice-changing clinical trial in our field, demonstrating that fractionated radiosurgery not only reduces recurrence after surgery for large brain metastases but may also improve overall survival," says Robert Mutter, M.D., chair of research in the Department of Radiation Oncology and co-leader of the Novel Therapeutics and Therapeutic Modalities Research Program at Mayo Clinic Comprehensive Cancer Center.

For more information, funding and authors, read the ASTRO abstract.