2241 - Neurocognitive Outcomes in Patients with Brain Metastases: A Systematic Review of Past Findings and Future Directions
Presenter(s)
T. Bou Dargham1, S. F. Winter2, K. Batich1, K. Gehring3, M. W. Parsons4, J. Dietrich2, T. C. Mullikin5, Z. J. Reitman5, S. R. Floyd5, J. P. Kirkpatrick5, P. W. Sperduto5, J. A. Hattangadi-Gluth6, H. A. Shih7, P. D. Brown8, M. P. Mehta9, E. P. Sulman5, K. B. Peters1, and E. J. Vaios5; 1Department of Neurosurgery, Duke University School of Medicine, Durham, NC, 2Department of Neurology, Division of Neuro-Oncology, Massachusetts General Hospital, Boston, MA, 3Department of Cognitive Neuropsychology, Tilburg University, Tilburg, Netherlands, 4Pappas Center for Neuro-Oncology and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, 5Department of Radiation Oncology, Duke University School of Medicine, Durham, NC, 6Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 7Department of Radiation Oncology, Mass General Brigham / Massachusetts General Hospital, Boston, MA, 8Department of Neurologic Surgery,, Rochester, MN, 9Department of Oncological Sciences, Herbert Wertheim College of Medicine, Florida International University, Miami, FL
Purpose/Objective(s):
Multi-modality therapy has significantly improved overall survival for some subsets of patients with brain metastases. However, neurocognitive sequelae remain a major challenge. While advances in radiation treatment have reduced toxicity, the potential interaction with targeted therapy and immunotherapy and the consequent impact on neurocognitive outcomes are poorly characterized. We aimed to summarize the existing data on cognitive outcomes in patients with brain metastases in the era of modern combined-modality therapy.Materials/Methods:
This systematic review adhered to PRISMA guidelines and included clinical trials reporting neurocognitive outcomes (including self-reported, objectively measured, and screening outcomes) in patients with brain metastases receiving radiotherapy with or without concurrent systemic therapies. References were identified through PubMed/Medline, EMBASE, and Web of Science searches from database inception through December 31, 2024 using pre-defined MeSH term-based search strategies. A two-step manual search and data extraction was completed independently by two reviewers, and discrepancies were resolved through discussion and consensus among the authors to ensure study quality and mitigate bias.Results:
39 studies from 1997-2024 involving 6,617 patients met inclusion criteria (n=27 whole-brain radiotherapy; n=12 radiosurgery), including six studies evaluating combined-modality therapy. Sixteen randomized trials that compared radiotherapy with or without concurrent systemic therapies were excluded, as they did not include dedicated neurocognitive assessments. Baseline neurocognitive deficits were frequently observed, and most randomized trials evaluating advanced radiotherapy techniques (hippocampal avoidance, radiosurgery) compared to whole-brain radiotherapy reported reduced cognitive decline and improved quality of life. There was no signal for increased toxicity with combined-modality therapy, including radiotherapy with concurrent systemic therapy, though evaluable trials were limited in number.Conclusion:
As survival improves for patients with brain metastases, cognitive function is an increasingly important outcome measure. While hippocampal avoidance whole-brain radiotherapy and radiosurgery have emerged as alternative options to mitigate long-term toxicities from whole-brain radiotherapy, the interaction of novel systemic therapies with radiotherapy and potential implications for neurocognition are understudied. There is an urgent need for targeted research to resolve existing evidence gaps to mitigate toxicity and improve quality of life. Recommended actions include integrating neurocognitive endpoints into oncology trials, expanding advanced radiotherapy and radioprotective strategies, and embedding routine cognitive screening and rehabilitation in neuro-oncology care pathways.