Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001

被引：490

作者：

Brown, Paul D. ^{[1
]}

Gondi, Vinai ^{[2
]}

Pugh, Stephanie ^{[3
]}

Tome, Wolfgang A. ^{[4
]}

Wefel, Jeffrey S. ^{[5
]}

Armstrong, Terri S. ^{[6
]}

Bovi, Joseph A. ^{[7
]}

Robinson, Cliff ^{[8
]}

Konski, Andre ^{[9
]}

Khuntia, Deepak ^{[10
]}

Grosshans, David ^{[5
]}

Benzinger, Tammie L. S. ^{[8
]}

Bruner, Deborah ^{[11
]}

Gilbert, Mark R. ^{[6
]}

Roberge, David ^{[12
]}

Kundapur, Vijayananda ^{[13
]}

Devisetty, Kiran ^{[14
]}

Shah, Sunjay ^{[15
]}

Usuki, Kenneth ^{[16
]}

Anderson, Bethany Marie ^{[17
]}

Stea, Baldassarre ^{[18
]}

Yoon, Harold ^{[19
]}

Li, Jing ^{[5
]}

Laack, Nadia N. ^{[1
]}

Kruser, Tim J. ^{[20
]}

Chmura, Steven J. ^{[21
]}

Shi, Wenyin ^{[22
]}

Deshmukh, Snehal ^{[3
]}

Mehta, Minesh P. ^{[23
]}

Kachnic, Lisa A. ^{[24
]}

机构：

[1] Mayo Clin, Rochester, MN USA

[2] Warrenville & Northwestern Med Proton Ctr, Northwestern Med Canc Ctr, Warrenville, IL USA

[3] NRG Oncol Stat & Data Management Ctr, Philadelphia, PA USA

[4] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA

[5] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[6] NCI, Ctr Canc Res, Bethesda, MD 20892 USA

[7] Froedtert & Med Coll Wisconsin, Milwaukee, WI USA

[8] Washington Univ, St Louis, MO 63110 USA

[9] Chester Cty Hosp, W Chester, PA USA

[10] Eden Med Ctr, East Bay Radiat Oncol Ctr, Castro Valley, CA USA

[11] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA

[12] CHUM Hotel Dieu Montreal, Montreal, PQ, Canada

[13] Saskatoon Canc Ctr, Saskatoon, SK, Canada

[14] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA

[15] Community Oncol Res Program, ChristianaCare Natl Canc Inst, Newark, DE USA

[16] Univ Rochester, Rochester, NY USA

[17] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA

[18] Univ Arizona, Med Ctr Univ Campus, Tucson, AZ USA

[19] NCI, Heartland Canc Res, Community Oncol Res Program, Decatur, IL USA

[20] Northwestern Mem Hosp, Chicago, IL 60611 USA

[21] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60637 USA

[22] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA

[23] Miami Canc Inst, Miami, FL USA

[24] Vanderbilt Univ, Med Ctr, Ingram Canc Ctr, Nashville, TN USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2020年 / 38卷 / 10期

关键词：

STEREOTACTIC RADIOTHERAPY; NEUROCOGNITIVE FUNCTION; RADIATION; TESTS;

D O I：

10.1200/JCO.19.02767

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSERadiation 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.METHODSThis 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.RESULTSBetween 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).CONCLUSIONHA-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. (c) 2020 by American Society of Clinical Oncology

引用

页码：1019 / +

页数：12

共 50 条

[1] NRG Oncology CC001: A phase III trial of hippocampal avoidance (HA) in addition to whole-brain radiotherapy (WBRT) plus memantine to preserve neurocognitive function (NCF) in patients with brain metastases (BM).
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[2] PRESERVATION OF NEUROCOGNITIVE FUNCTION (NCF) WITH HIPPOCAMPAL AVOIDANCE DURING WHOLE-BRAIN RADIOTHERAPY (WBRT) FOR BRAIN METASTASES: PRELIMINARY RESULTS OF PHASE III TRIAL NRG ONCOLOGY CC001
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[J]. NEUROSURGERY, 2019, 66 : 137 - 138
[4] Preservation of Neurocognitive Function (NCF) with Conformal Avoidance of the Hippocampus during Whole-Brain Radiotherapy (HA-WBRT) for Brain Metastases: Preliminary Results of Phase III Trial NRG Oncology CC001
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Anderson, B. M.
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[J]. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2018, 102 (05): : 1607 - 1607
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Devisetty, K.
Shah, S. A.
Usuki, K. Y.
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[J]. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2019, 105 (01): : S12 - S13
[6] PRESERVATION OF NEUROCOGNITIVE FUNCTION & PATIENT-REPORTED SYMPTOMS WITH HIPPOCAMPAL AVOIDANCE (HA) DURING WHOLE-BRAIN RADIOTHERAPY (WBRT) FOR BRAIN METASTASES: LONG-TERM RESULTS OF NRG ONCOLOGY CC001
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[7] Hippocampal avoidance whole-brain radiotherapy without memantine in preserving neurocognitive function for brain metastases: a phase II blinded randomized trial
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[10] Neurocognitive Outcomes for Patients With Brain Metastasis in the Modern Era: Benefit of Treatment With Hippocampal Avoidance Whole-Brain Radiotherapy Plus Memantine
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