Hippocampal avoidance whole-brain radiotherapy without memantine in preserving neurocognitive function for brain metastases: a phase II blinded randomized trial

Wen-Chi Yang; Ya-Fang Chen; Chi-Cheng Yang; Pei-Fang Wu; Hsing-Min Chan; Jenny Ling-Yu Chen; Guann-Yiing Chen; Jason Chia-Hsien Cheng; Sung-Hsin Kuo; Feng-Ming Hsu

doi:10.1093/neuonc/noaa193

Hippocampal avoidance whole-brain radiotherapy without memantine in preserving neurocognitive function for brain metastases: a phase II blinded randomized trial

Neuro Oncol. 2021 Mar 25;23(3):478-486. doi: 10.1093/neuonc/noaa193.

Authors

Wen-Chi Yang^{1

2

3}, Ya-Fang Chen^{4

5}, Chi-Cheng Yang^{6

7}, Pei-Fang Wu⁸, Hsing-Min Chan¹, Jenny Ling-Yu Chen^{1

4}, Guann-Yiing Chen^{1

5}, Jason Chia-Hsien Cheng^{1

2

3}, Sung-Hsin Kuo^{1

2

3}, Feng-Ming Hsu^{1

2

3}

Affiliations

¹ Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
² Graduate Institute of Oncology, National Chengchi University, Taipei, Taiwan.
³ Cancer Research Center, National Chengchi University, Taipei, Taiwan.
⁴ Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan.
⁵ Department of Medical Imaging, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan.
⁶ Department of Psychology, National Chengchi University, Taipei, Taiwan.
⁷ Holistic Mental Health Center, Taipei City Hospital, Taipei, Taiwan.
⁸ Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.

Abstract

Background: Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) shows potential for neurocognitive preservation. This study aimed to evaluate whether HA-WBRT or conformal WBRT (C-WBRT) is better for preserving neurocognitive function.

Methods: This single-blinded randomized phase II trial enrolled patients with brain metastases and randomly assigned them to receive HA-WBRT or C-WBRT. Primary endpoint is decline of the Hopkins Verbal Learning Test-Revised (HVLT-R) delayed recall at 4 months after treatment. Neurocognitive function tests were analyzed with a mixed effect model. Brain progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.

Results: From March 2015 to December 2018, seventy patients were randomized to yield a total cohort of 65 evaluable patients (33 in the HA-WBRT arm and 32 in the C-WBRT arm) with a median follow-up of 12.4 months. No differences in baseline neurocognitive function existed between the 2 arms. The mean change of HVLT-R delayed recall at 4 months was -8.8% in the HA-WBRT arm and +3.8% in the C-WBRT arm (P = 0.31). At 6 months, patients receiving HA-WBRT showed favorable perpetuation of HVLT-R total recall (mean difference = 2.60, P = 0.079) and significantly better preservation of the HVLT-R recognition-discrimination index (mean difference = 1.78, P = 0.019) and memory score (mean difference = 4.38, P = 0.020) compared with patients undergoing C-WBRT. There were no differences in Trail Making Test Part A or Part B or the Controlled Oral Word Association test between the 2 arms at any time point. There were no differences in brain PFS or OS between arms as well.

Conclusion: Patients receiving HA-WBRT without memantine showed better preservation in memory at 6-month follow-up, but not in verbal fluency or executive function.

Trial registration: ClinicalTrials.gov NCT02393131.

Keywords: brain metastasis; hippocampus; neuropsychological tests; single blind method; whole brain radiotherapy.

Publication types

Clinical Trial, Phase II
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Brain Neoplasms* / radiotherapy
Cranial Irradiation / adverse effects
Hippocampus
Humans
Memantine / therapeutic use
Radiation Injuries*

Substances

Memantine

Associated data

ClinicalTrials.gov/NCT02393131