Treatment for Brain Metastases With Stereotactic Radiation vs Hippocampal-Avoidance Whole Brain Radiation
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Importance: Brain metastases are common in patients with cancer, and radiation is often used for management. Among patients with more than 4 brain metastases, the effects of stereotactic radiation targeting only individual tumors, compared with whole brain radiation with hippocampal avoidance, which radiates both tumors and normal brain, remain unknown. Objective: To determine whether stereotactic radiation improves symptom severity and interference with daily functioning, compared with whole brain radiation with hippocampal avoidance. Design, Setting, and Participants: Phase 3, open-label, randomized clinical trial conducted at 4 United States-based centers. Eligible patients had 5 to 20 brain metastases and no prior brain-directed radiation. Enrollment occurred between April 11, 2017, and May 17, 2024 (final follow-up, March 18, 2025). Intervention: Stereotactic radiation, compared with whole brain radiation with hippocampal avoidance. Main Outcomes and Measures: Mean weighted patient-reported symptom severity and interference score change over 6 months postbaseline relative to baseline using the MD Anderson Symptom Inventory-Brain Tumor instrument (scale, 0-10; score change range, -10 to 10; -10 = best). A clinically meaningful Δ was defined as 0.98. Results: Of 196 randomized patients (mean age, 61 years; 129 [66%] female; 176 [90%] White; median number of brain metastases, 14 [IQR, 11-18]; 49 [25%] with prior neurosurgical resection), 83 (42%) completed the 6-month assessment. For the primary outcome, between baseline and postbaseline assessments through the 6-month follow-up, stereotactic radiation changed the weighted composite MD Anderson Symptom Inventory-Brain Tumor score from 2.69 to 2.37 (mean change, -0.32) and hippocampal-avoidance whole brain radiation changed the score from 2.29 to 3.03 (mean change, 0.74) (mean difference, -1.06 [95% CI, -1.54 to -0.58]; P < .001). Related grade 3-5 adverse events occurred in 12 patients (12%) in the stereotactic radiation group and 13 patients (13%) in the hippocampal-avoidance whole brain radiation group; grade 1-3 fatigue was most frequent (27 [28%] vs 43 [44%], respectively). Conclusions and Relevance: In patients with 5 to 20 brain metastases, these findings support stereotactic radiation over hippocampal-avoidance whole brain radiation to improve symptoms and interference with daily functioning, key components of quality of life. Trial Registration: ClinicalTrials.gov Identifier: NCT03075072.
Source: JAMA
Authors: Ayal A. Aizer, Kee-Young Shin, Paul J. Catalano, Ivy Ricca, Marciana Johnson, Grant Benham, Kristin Roper, Beverly Spicer, Eileen Mann, Jennifer Nosker, Michael W. Parsons, Mallika L. Mendu, Jaroslaw Hepel, Fallon Chipidza, Monica Krishnan, Diana D. Shi, Nayan Lamba, Itai Pashtan, Luke Peng, Brian Alexander, Paul D. Brown, Patrick Y. Wen, Daphne A. Haas-Kogan, Rifaquat Rahman, Shyam Tanguturi
Institutions: Brigham and Women's Hospital, Dana-Farber Cancer Institute, Dana-Farber Brigham Cancer Center, Harvard University, South Shore Hospital, Milford Hospital, Massachusetts General Hospital, Mass General Brigham, Brown University, Rhode Island Hospital, Mayo Clinic, Center for Neuro-Oncology
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7130516387