In a phase 3 trial of 242 patients whose cancer had spread to the brain, splitting stereotactic radiosurgery into three to five sessions after a tumor was surgically removed lowered the chance that the cancer returned at the surgical site, compared with a single high-dose session.
The results were presented Sept. 28 at the American Society for Radiation Oncology (ASTRO) annual meeting in Boston. They have not yet been published in a peer-reviewed journal.
For patients and families facing brain metastases, the choice between one visit and several can feel like a scheduling question, especially when a loved one is already exhausted from surgery. The trial suggests it may also affect how well the cancer is controlled.
Single-Session Versus Split-Dose Radiosurgery
Brain metastases are tumors that start elsewhere in the body, often the lung, breast, or skin, and spread to the brain. When a metastasis is large, surgeons often remove it. Radiation to the cavity afterward aims to kill remaining cancer cells.
Stereotactic radiosurgery, or SRS, involves no incision despite its name. It uses tightly focused beams to deliver high doses to a small target. It can be given in a single session or split across several sessions, a method called fractionated SRS. Splitting the dose may allow a stronger total dose to the target while giving surrounding brain tissue time to recover between treatments.
The trial, called Alliance A071801, compared the two approaches directly. Patients had one to four brain metastases, including at least one larger than 2 centimeters that had been surgically removed. They were enrolled between October 2019 and October 2022 and followed for a median of about four years, according to the ASTRO session abstract. The single-session group received 12 to 20 Gy depending on cavity size, while the split-dose group received 27 Gy over three sessions or 30 Gy over five.
Recurrence, Survival and Side Effect Figures
At one year, 87% of patients in the split-dose group had no recurrence at the surgical site, compared with 81% in the single-session group. That difference was statistically significant, according to ASTRO's news release.
Median overall survival was 29 months with the split-dose approach and 20 months with single-session treatment, and patients who received fractionated treatment had a 31% lower risk of death. New growth elsewhere in the brain occurred in 4% of the split-dose group and 11% of the single-session group, but that difference was not statistically significant.
Side effects were similar between the groups. Radiation necrosis, a form of tissue damage that can cause swelling or neurological symptoms, occurred in 14% of the split-dose group and 10% of the single-session group. Brain swelling occurred in 8% and 9%, respectively.
"We now have the strongest evidence to date that three to five sessions should be considered a standard postoperative treatment for patients with larger brain metastases," said Dr. Ayal A. Aizer, a radiation oncologist at Mass General Brigham and Dana-Farber Cancer Institute who presented the study.
Dr. Robert Mutter, chair of research in the Department of Radiation Oncology at Mayo Clinic, which helped run the trial, went further. "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," he told the Mayo Clinic News Network.
MedicalDaily Evidence Check
This was a randomized phase 3 trial, the strongest type of evidence for comparing treatments, run through the NCI-sponsored Alliance for Clinical Trials in Oncology. It included 242 patients, which is modest for survival comparisons. The results come from a conference presentation, and the full data have not yet gone through journal peer review, so the numbers could be refined.
The main finding concerns recurrence at the surgical site. The survival difference is encouraging, but survival in these patients depends heavily on their original cancer and other treatments, so that result deserves more cautious reading. The trial applies to patients whose removed tumor was larger than 2 centimeters, not to every patient with brain metastases.
Treatment guidelines have not yet changed based on this trial. Guideline committees typically wait for the full publication and for longer-term data on memory and quality of life, which matter to patients as much as tumor control. The trial also did not test split-dose radiosurgery in patients whose metastases were not removed or in those with more than four lesions.
Questions for the Care Team
Patients preparing for radiation after brain metastasis surgery can ask whether single-session or fractionated SRS is planned and why. Tumor size, location, the number of lesions, and overall health all shape that decision.
Split-dose treatment means more visits, usually three to five over one to two weeks. That can be harder for patients who live far from a radiation center, rely on others for rides or are managing fatigue. Asking early about transportation help, scheduling and lodging programs can make the plan workable, and checking with the insurer can clarify costs.
After treatment, new or worsening headaches, weakness, seizures, confusion or vision changes should be reported to the care team right away, since these can signal swelling, recurrence or radiation effects. MedicalDaily will report when the full trial results are published.
Key Questions Answered
What did the trial compare?
Single-session stereotactic radiosurgery versus the same technique split into three to five sessions after surgery to remove a brain metastasis larger than 2 centimeters.
What did it find?
At one year, 87% of the split-dose group had no recurrence at the surgical site, compared with 81% of the single-session group.
Did survival differ?
Median survival was 29 months with split-dose treatment and 20 months with single-session treatment.
Were side effects worse with more sessions?
Side effects were similar. Radiation necrosis occurred in 14% of the split-dose group versus 10% of the single-session group.
Has this been peer reviewed?
Not yet. The results were presented at the ASTRO annual meeting and are awaiting journal publication.
Who does this apply to?
Patients with one to four brain metastases who had a tumor larger than 2 centimeters surgically removed.
Published by Medicaldaily.com
