An initial report of memory avoidance whole brain radiotherapy to treat brain metastases

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.

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.

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.

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).