An initial report of memory avoidance whole brain radiotherapy to treat brain metastases
In brief
Memory-avoidance whole brain radiotherapy reduces 3-month cognitive decline to 17%
In a phase-2 cohort of 29 patients with more than 15 brain metastases, sparing the hippocampus plus additional memory-critical structures lowered neurocognitive decline at three months to 17.2% (vs ~50% historically) and to 48.3% at six months. The approach was safe, with only one substructure failure, and a direct trial against standard hippocampal avoidance is pending.
- Journal
- Neuro-oncology advances (Q1)
- Published
- 13 August 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Joshua D Palmer, Erica L Dawson, Yilun Sun, Jiawei Yu, Khaled Dibs, Alex R Ritter, et al.
- PMID
- 42677319
- DOI
- 10.1093/noajnl/vdag211
Why clinicians should know about it
- Picked for Radiation Oncology (paper of the day, 3 September 2026): Memory‑avoidance WBRT, low cognitive decline
Abstract
BACKGROUND: Hippocampal avoidance whole brain radiotherapy (HA-WBRT) with memantine is standard of care for patients with extensive brain metastases requiring radiation. However, other brain structures have critical memory and cognition roles, including the corpus callosum, fornix, amygdala, hypothalamus, and pituitary. A subset of patients enrolled on a Phase 2 Randomized Controlled Trial received an advanced "memory-avoidance" WBRT (MA-WBRT) approach that spared these substructures in addition to the hippocampus. METHODS: Patients with >15 brain metastases were enrolled in the ATHENA Trial and received MA-WBRT. All patients received 30 Gy in 10 fractions of MA-WBRT and were prescribed memantine. Cognition was measured by Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association Test, and Trail Making Test A/B, with cognitive decline defined as decline on at least one assessment using the reliable change index. RESULTS: Between August 2022 and May 2024, 29 patients were prescribed MA-WBRT. Decline in neurocognitive function at 3 and 6 months for patients receiving MA-WBRT was 17.2% and 48.3%, respectively. There was only 1 failure in a memory avoidance substructure (occurring in the right fornix 10 months after enrollment), and this was associated with concurrent distant intracranial failure outside the memory avoidance zone. CONCLUSIONS: The cognitive decline rates of 17.2% and 48.3% at 3 and 6 months for patients receiving MA-WBRT compare favorably to the 3- and 6-month cognitive decline rates of 50% and 60% seen on NRG CC001. A direct comparison of MA-WBRT plus memantine vs. HA-WBRT plus memantine is forthcoming in a randomized phase 2 trial (NCT07248228).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.