Stereotactic Radiation Improves Quality of Life in Patients With Multiple Brain Metastases: JAMA
In a phase III randomized trial involving patients with five to 20 brain metastases, stereotactic radiation demonstrated better quality-of-life outcomes compared with hippocampal-avoidance whole-brain radiation (HA-WBRT). While prior randomized data in this population were limited, the study showed meaningful benefits in patient-reported quality of life. However, no significant differences were observed between the two approaches in post-treatment general neurocognitive screening, self-reported cognitive symptoms, or motor dexterity, indicating comparable cognitive preservation between strategies. The study was published in JAMA by Ayal A. and colleagues.
This open-label phase 3 randomized clinical trial took place at four research centers in the United States. The inclusion criteria included patients with 5 to 20 brain metastases and no prior brain-directed radiation therapy. The study took place between April 11, 2017, and May 17, 2024, with the final follow-up on March 18, 2025.
A total of 196 patients were randomly assigned to the study. The mean age was 61 years, with 129 (66%) female patients and 176 (90%) White patients. The median number of brain metastases was 14, ranging from 11 to 18 lesions in the interquartile range. Forty-nine (25%) patients had prior neurosurgical resection. Of the 196 patients, 83 (42%) completed the 6-month patient-reported outcome assessment.
Participants were randomly assigned to receive stereotactic radiation therapy directed at individual tumors or whole brain radiation with hippocampal avoidance. The primary outcome measure was the mean weighted change in patient-reported symptom severity and interference with daily functioning at six months, assessed with the MD Anderson Symptom Inventory-Brain Tumor questionnaire. Scores vary from 0 to 10, and the change varies from −10 to 10, with a more negative change indicating improvement. A clinically important difference was specified as a change of 0.98 points.
Key findings
From baseline to the 6-month follow-up, the mean weighted composite score decreased by 0.32 in the stereotactic radiation group, from 2.69 to 2.37, while in the hippocampal-avoidance whole brain radiation group, the score increased by 0.74, from 2.29 to 3.03.
The mean difference between the groups was −1.06 (95% confidence interval, −1.54 to −0.58; P < 0.001), which crossed the threshold of 0.98.
In terms of safety, the incidence of grade 3 to 5 adverse events related to treatment was 12 patients (12%) in the stereotactic radiation group and 13 patients (13%) in the hippocampal-avoidance whole brain radiation group.
Fatigue was the most common adverse event, occurring as grade 1 to 3 fatigue in 27 patients (28%) in the stereotactic radiation group compared with 43 patients (44%) in the whole brain radiation group.
In patients with 5 to 20 brain metastases, stereotactic radiation therapy led to greater improvements in symptoms and interference with daily functioning than hippocampal avoidance whole brain radiation therapy. The mean difference of −1.06 points on the MD Anderson Symptom Inventory-Brain Tumor scale exceeded the threshold for clinical significance and was consistent with equivalent safety outcomes. These results confirm stereotactic radiation therapy as the preferred treatment for improving quality of life.
Reference:
Aizer AA, Shin K, Catalano PJ, et al. Treatment for Brain Metastases With Stereotactic Radiation vs Hippocampal-Avoidance Whole Brain Radiation: A Randomized Clinical Trial. JAMA. Published online February 19, 2026. doi:10.1001/jama.2026.0076
