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Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001
Author
Brown, Paul DGondi, Vinai
Pugh, Stephanie
Tome, Wolfgang A
Wefel, Jeffrey S
Armstrong, Terri S
Bovi, Joseph A
Robinson, Cliff
Konski, Andre
Khuntia, Deepak
Grosshans, David
Benzinger, Tammie L S
Bruner, Deborah
Gilbert, Mark R
Roberge, David
Kundapur, Vijayananda
Devisetty, Kiran
Shah, Sunjay
Usuki, Kenneth
Anderson, Bethany Marie
Stea, Baldassarre
Yoon, Harold
Li, Jing
Laack, Nadia N
Kruser, Tim J
Chmura, Steven J
Shi, Wenyin
Deshmukh, Snehal
Mehta, Minesh P
Kachnic, Lisa A
Affiliation
Univ Arizona, Med Ctr Univ CampusIssue Date
2020-02-14
Metadata
Show full item recordPublisher
AMER SOC CLINICAL ONCOLOGYCitation
Brown, P. D., Gondi, V., Pugh, S., Tome, W. A., Wefel, J. S., Armstrong, T. S., ... & Grosshans, D. (2020). Hippocampal avoidance during whole-brain radiotherapy plus memantine for patients with brain metastases: Phase III trial NRG Oncology CC001. Journal of Clinical Oncology, 38(10), 1019-1029.Journal
JOURNAL OF CLINICAL ONCOLOGYRights
Copyright © 2020 American Society of Clinical Oncology. All rights reserved.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
PURPOSE Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition. METHODS This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine. The primary end point was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests. Secondary end points included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported symptom burden. RESULTS Between July 2015 and March 2018, 518 patients were randomly assigned. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; P = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% v 40.4%; P = .01) and learning and memory at 6 months (11.5% v 24.7% [P = .049] and 16.4% v 33.3% [P = .02], respectively). Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue (P = .04), less difficulty with remembering things (P = .01), and less difficulty with speaking (P = .049) and using imputed data, less interference of neurologic symptoms in daily activities (P = .008) and fewer cognitive symptoms (P = .01). CONCLUSION HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.Note
12 month embargo; published online: 14 February 2020ISSN
0732-183XPubMed ID
32058845Version
Final published versionae974a485f413a2113503eed53cd6c53
10.1200/JCO.19.02767
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