RDTA-06 AN INITIAL REPORT OF MEMORY AVOIDANCE WHOLE BRAIN RADIOTHERAPY TO TREAT BRAIN METASTASES: A PROSPECTIVE PHASE 2 TRIAL

Abstract A common approach for patients with extensive brain metastases requiring radiation is hippocampal avoidance whole brain radiotherapy (HA-WBRT) prescribed with memantine; this was proven reduce the incidence of cognitive decline in NRG CC001. Other brain structures with important roles in memory and cognition include the corpus callosum, fornix, amygdala, hypothalamus, and pituitary. A subset of patients enrolled on a Phase 2 Randomized Controlled Trial (NCT05503251) received an advanced “memory-avoidance” WBRT (MA-WBRT) approach that spared these substructures in addition to the hippocampus. All patients with > 15 brain metastases on this trial received MA-WBRT, 30 Gy in 10 fractions, 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 reliable change index. Between August 2022 and May 2024, 29 patients received MA-WBRT. The median overall survival or time to last follow up was 7.9 months. The three- and six-month decline in neurocognitive function for patients receiving MA-WBRT was 17.2% and 48.3%, respectively. There was only one 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 three and six months for patients receiving MA-WBRT compare very favorably to three and six-month cognitive decline rates of 50% and 60% that were seen on NRG CC001. Additionally, MA-WBRT does not appear to significantly increase the risk of intracranial failure compared to HA-WBRT. Further evaluation of the delayed impact (> 6 months) of MA-WBRT on cognitive function will be reported when data are available. A direct comparison of MA-WBRT plus memantine vs. HA-WBRT plus memantine is forthcoming in a randomized phase 2 trial.