HipSter
(2026)Objective
To determine whether stereotactic radiation improves symptom severity and interference with daily functioning compared with hippocampal-avoidance whole brain radiation in patients with 5 to 20 brain metastases.
Study Summary
• Grade 3-5 related adverse events were similar (12% stereotactic vs 13% hippocampal-avoidance WBRT)
• Grade 1-3 fatigue was less frequent with stereotactic radiation (28% vs 44%)
Intervention
Stereotactic radiation targeting individual tumors vs hippocampal-avoidance whole brain radiation
Inclusion Criteria
Patients with 5 to 20 brain metastases and no prior brain-directed radiation
Study Design
Arms: Stereotactic radiation vs Hippocampal-avoidance whole brain radiation (total n=196)
Patients per Arm: 196 total (arm-level n not reported in abstract)
Outcome
• Related grade 3-5 adverse events: 12% vs 13%
• Grade 1-3 fatigue: 28% (stereotactic) vs 44% (HA-WBRT)
Bottom Line
In patients with 5 to 20 brain metastases, stereotactic radiation improved patient-reported symptoms and interference with daily functioning compared with hippocampal-avoidance whole brain radiation, supporting stereotactic radiation as the preferred approach.
Major Points
- In 196 patients with 5 to 20 brain metastases, stereotactic radiation produced a mean change in the composite MDASI-BT score of −0.32 vs +0.74 with hippocampal-avoidance whole brain radiation (mean difference −1.06; 95% CI, −1.54 to −0.58; P<.001).
- The between-group difference exceeded the prespecified clinically meaningful threshold of 0.98.
- Related grade 3-5 adverse events were similar between groups (12% stereotactic vs 13% HA-WBRT).
- Grade 1-3 fatigue was less frequent with stereotactic radiation (28% vs 44%).
- Findings support stereotactic radiation over hippocampal-avoidance whole brain radiation in patients with 5 to 20 brain metastases to improve symptoms and interference with daily functioning.
Study Design
- Study Type
- Phase 3, open-label, randomized clinical trial
- Randomization
- Yes
- Blinding
- Open-label
- Sample Size
- 196
- Follow-up
- Final follow-up March 18, 2025; primary outcome assessed over 6 months postbaseline
- Centers
- 4
- Countries
- United States
Primary Outcome
Definition: Mean weighted patient-reported symptom severity and interference score change using the MD Anderson Symptom Inventory–Brain Tumor (MDASI-BT) instrument (composite score range, −10 to 10; −10 = best)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Score changed from 2.29 to 3.03 (mean change +0.74) with hippocampal-avoidance whole brain radiation | Score changed from 2.69 to 2.37 (mean change −0.32) with stereotactic radiation | - (−1.54 to −0.58) | <.001 |
Limitations & Criticisms
- Open-label design may have influenced patient-reported outcomes.
- Only 83 of 196 patients (42%) completed the 6-month assessment, raising concern for attrition bias.
- Conducted at only 4 US-based centers, which may limit generalizability.
- Population was 90% White, limiting generalizability across racial/ethnic groups.
- Long enrollment period (2017-2024) spans evolving systemic therapy practices.
Citation
Aizer AA, et al. Treatment for Brain Metastases With Stereotactic Radiation vs Hippocampal-Avoidance Whole Brain Radiation: A Randomized Clinical Trial. JAMA. 2026;335(13):1127-1136.