Early Integrated Neuropsychological Care for Patients with Brain Metastases: A Randomized Controlled Trial (ATHENA Trial).

Authors

Haley K Perlow, Erica L Dawson, Yilun Sun, Jiawei Yu, Khaled Dibs, Alex R Ritter, Daniel Boulter, Ansel P Nalin, Raj Singh, Sasha J Beyer, Evan M Thomas, Simeng Zhu, Dukagjin M Blakaj, John C Grecula, Raju R Raval, Shayla Vazquez, Samantha Whitman, Carolyn J Presley, Clement Pillainayagam, Pierre Giglio, Joshua D Palmer

Published in

International journal of radiation oncology, biology, physics. Jul 18, 2026. Epub Jul 18, 2026.

Abstract

Decline of quality of life (QOL) and cognitive function is common for brain metastases patients receiving radiotherapy but there is currently no standard of care for addressing those symptoms. This phase 2 randomized controlled trial examined the efficacy of early neuropsychological evaluation and integration to preserve QOL and cognition for patients treated with radiation for brain metastases.
Patients with brain metastases seen in a radiation oncology department were eligible for inclusion and randomized 1:1 to neuropsychology integration versus standard of care. The neuropsychology integration involved 5 appointments over a 3-month period beginning prior to radiotherapy treatment initiation. Quality of life was measured with FACT-Br and EORTC QLQ-C30 assessments. Cognition was measured by the Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association Test, and Trail Making Test A/B. Depression (PHQ-9) and anxiety (GAD-7) assessments were also collected. The primary endpoint was change in QOL three months after completion of radiotherapy measured by FACT-Br. Longitudinal outcomes were analyzed using linear mixed-effects models adjusting for baseline score and radiation type.
From August 2022 to June 2024, 110 patients were enrolled. The median age and Karnofsky Performance Status were 62.5 (IQR 54, 70) and 90 (IQR 80,90), respectively. A plurality of patients (43%) had primary lung cancer, and most patients (74%) had ≤15 brain metastases. With a median follow-up of 21.1 months (95% CI: 16.2-25.5), the primary endpoint was not met (estimated difference 0.27, SE=0.19, p=0.15). In exploratory analyses at 9 months, FACT-Br scores were higher in the integration arm (0.63, p=0.006). There were no differences in neurocognitive function between arms.
In this phase 2 randomized trial, the primary endpoint of improved FACT-Br QOL at 3 months after radiation therapy was not met. Exploratory findings at later timepoints suggest potential benefits in QOL.

PMID:
42471047
Bibliographic data and abstract were imported from PubMed on 19 Jul 2026.

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