Effect of early integrated neuropsychological care in patients with brain metastases: A phase 2 randomized controlled trial (ATHENA trial).

Abstract

2031 Background: Advancements in radiotherapy delivery through both hippocampal sparing whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) can better preserve QOL and reduce cognitive decline. However, even patients treated with advanced brain radiotherapy techniques have a reduction in their QOL and cognitive abilities either due to their radiation treatment, systemic therapy, or progression of disease. This Phase 2 Randomized Controlled Trial ( NCT05503251 ) aims to evaluate the impact of a neuropsychological evaluation and intervention with a certified neuropsychologist on QOL and cognitive function for brain metastases patients treated with radiotherapy. Methods: Brain metastases patients were randomized 1:1 to either neuropsychology evaluation and intervention plus brain radiotherapy or brain radiotherapy alone. The intervention arm included five appointments with the neuropsychology team for testing, evaluation, and counseling over a three-month period. Patients with any number of brain metastases and an estimated survival of ≥ 6 months were included. Exclusion criteria included prior WBRT and pre-existing mental disability. Stratification factors for randomization were Karnofsky performance status (KPS, > 70 vs. ≤ 70) and radiation cohort ( > 15 brain metastases received WBRT, ≤15 received SRS). All patients receiving WBRT were prescribed memantine. The primary endpoint was deterioration of QOL at 3 months as measured by Fact-Br. Repeated measures analysis of variance was used to measure QOL. 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. Results: Between August 2022 and June 2024, 110 patients were randomized. Baseline characteristics were balanced between arms and included a median KPS of 90 (IQR 80, 90), median age of 62.5 (IQR 54, 70), 53% female patients, 43% of patients with a primary lung cancer, and most patients (74%) with ≤15 brain metastases. The median overall survival or time to last follow-up was 8.5 months. The primary endpoint, deterioration of QOL at 3 months, was not different between the control and intervention arms (p = 0.93). Cognitive decline differences at 3 months were not significant between the control and intervention arms (24.1% vs. 27.3%, p = 0.33). Additionally, there were no differences at 3 months with verbal fluency, executive function, immediate recall, delayed recall, or delayed recognition between arms. Conclusions: This study did not meet its primary endpoint, better preserved QOL at 3 months for patients receiving early integrated neuropsychological care. Further evaluation of the delayed impact ( > 6 months) of neuropsychology intervention on QOL and cognitive function will be reported when data are available. Clinical trial information: NCT05503251 .