103 - An Initial Report of Memory Avoidance Whole Brain Radiotherapy to Treat Brain Metastases: A Prospective Phase 2 Trial
Presenter(s)
J. D. Palmer1, E. Dawson2, K. Dibs1, A. Ritter3, Y. Sun4, D. Boulter5, A. Nalin6, R. Singh1, S. Beyer1, E. M. Thomas1, S. Zhu1, D. M. Blakaj1, J. C. Grecula1, R. Raval1, S. Vazquez2, S. Whitman2, C. Presley7, C. Pillainayagam8, P. Giglio9, and H. K. Perlow10; 1Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, 2Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, 3The Ohio State University, Columbus, OH, 4Department of Population and Quantitative Health Sciences, School of Medicine, Cleveland, OH, 5Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, 6Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 7Department of Medical Oncology, The Ohio State University James Cancer Center, Columbus, OH, 8Department of Solid Tumor Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Columbus, OH, 9Division of Neuro-Oncology, Ohio State University, Columbus, OH, 10Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH
Purpose/Objective(s):
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. However, the majority of patients who receive HA-WBRT with memantine still experience cognitive decline. Other brain structures with important roles in memory and cognition include the corpus callosum, fornix, amygdala, hypothalamus, and pituitary. Notably, all of these structures have a low propensity for brain metastases and can potentially be spared without increasing the risk of relapse. 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.Materials/Methods:
All patients with > 15 brain metastases enrolled in a prospective clinical trial, which randomized patients to either neuropsychology evaluation and intervention plus brain radiotherapy or brain radiotherapy alone, received MA-WBRT. Exclusion criteria included prior WBRT, pre-existing mental disability, and metastases within the avoidance neurocognitive substructures. 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 reliable change index (the same tests and definition used in NRG CC001). The primary endpoint was improved cognition compared to NRG CC001.Results:
Between August 2022 and May 2024, 29 patients received MA-WBRT. Baseline characteristics included a median Karnofsky performance status (KPS) of 80 (IQR 70, 90), median age of 64 years (IQR 54, 69), 62% female patients, and a plurality of patients with a primary lung cancer (48%). 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.Conclusion:
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. (NCT05503251)