TY - JOUR
T1 - Hippocampal avoidance during whole-brain radiotherapy plus memantine for patients with brain metastases
T2 - Phase III trial NRG oncology CC001
AU - Brown, Paul D.
AU - Gondi, Vinai
AU - Pugh, Stephanie
AU - Tome, Wolfgang A.
AU - Wefel, Jeffrey S.
AU - Armstrong, Terri S.
AU - Bovi, Joseph A.
AU - Robinson, Cliff
AU - Konski, Andre
AU - Khuntia, Deepak
AU - Grosshans, David
AU - Benzinger, Tammie L.S.
AU - Bruner, Deborah
AU - Gilbert, Mark R.
AU - Roberge, David
AU - Kundapur, Vijayananda
AU - Devisetty, Kiran
AU - Shah, Sunjay
AU - Usuki, Kenneth
AU - Anderson, Bethany Marie
AU - Stea, Baldassarre
AU - Yoon, Harold
AU - Li, Jing
AU - Laack, Nadia N.
AU - Kruser, Tim J.
AU - Chmura, Steven J.
AU - Shi, Wenyin
AU - Deshmukh, Snehal
AU - Mehta, Minesh P.
AU - Kachnic, Lisa A.
N1 - Funding Information: Supported by National Cancer Institute grants UG1CA189867 (National Cancer Institute Community Oncology Research Program) and U10CA180868 (NRG Oncology Operations). Publisher Copyright: Copyright © 2020 American Society of Clinical Oncology. All rights reserved.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.19.02767
DO - 10.1200/JCO.19.02767
M3 - Article
C2 - 32058845
SN - 0732-183X
VL - 38
SP - 1019
EP - 1029
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 10
ER -