Hippocampal Avoidance Whole-brain Radiotherapy in Preservation of Neurocognitive Function for Brain Metastases: A Phase II Blinded Randomized Trial

Abstract

AbstractBackgroundHippocampal avoidance whole-brain radiotherapy (HA-WBRT) shows potential for neurocognitive preservation. This study aimed to evaluate whether HA-WBRT or conformal WBRT is better for preserving neurocognitive function.MethodsThis single-blinded randomized phase II trial enrolled patients with brain metastases and randomly assigned to receive HA-WBRT or conformal WBRT. Primary end point is the decline of 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 (BPFS) and overall survival (OS) were estimated using the Kaplan–Meier method.ResultsPatients were enrolled from March 2015 to December 2018 with a median follow-up of 12.4 months. A total of 70 patients were randomized. No differences in baseline neurocognitive function existed between the two arms. There were no differences in any neurocognitive assessments at four months. At six 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 conformal WBRT. There were no differences in TMT part A, part B, or the COWA test between the two arms at any time point. There were no differences in BPFS or OS between arms as well.ConclusionsPatients receiving HA-WBRT without Memantine showed better preservation in late verbal memory, but not in verbal fluency or executive function.