Patient-Reported Quality of Life and Functional Outcomes in A Phase II Blinded Randomized Trial of Hippocampal Avoidance Whole Brain Radiotherapy for Brain Metastases

Abstract

<h3>Purpose/Objective(s)</h3> This phase II blinded randomized trial investigated the neurocognitive outcomes of conformal whole brain radiotherapy (WBRT) with or without hippocampal avoidance for patients with brain metastases. Patients received hippocampal-avoidant WBRT had better preservation in late verbal memory measured by the Hopkins Verbal Learning Test-Revised. Here, we presented the patient-reported health-related quality of life (HRQOL) and functional outcomes. <h3>Materials/Methods</h3> Adult patients with brain metastases were randomized to receive hippocampal-avoidant conformal WBRT (HA-cWBRT) versus conformal WBRT without hippocampal avoidance (cWBRT) to 30 Gy in 10 fractions. Memantine was not used during or after WBRT. HRQOL was a secondary end point in the trial. HRQOL was assessed at baseline, 2, 4, 6, and every 3 months up to two years with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and Brain Cancer Module. The following six primary HRQOL function scales were considered: global health status; physical, cognitive, role, social, and emotional functioning. A ≥ 10-point difference from baseline is considered of clinical relevance. HRQOL results were compared at baseline and over time with mixed effects models adjusted for treatment arm, time, and interaction. Pearson correlation between function scales was performed. Statistical significance required <i>P</i> < 0.05. <h3>Results</h3> From March 2015 to November 2018, 70 patients were randomized and 65 patients (HA-cWBRT group, n = 33; cWBRT group, n = 32) completed protocol treatment. Compliance was 100% at baseline, 56.9% at 6 months, and dropped to 29.2% at 12 months. Thus, only the first year was analyzed. There were no differences in the six primary HRQOL function scales between the two arms at baseline. Patients in the cWBRT arm reported better HRQOL scores in cognitive functioning (<b>P</b> = 0.02), emotional functioning (<b>P</b> = 0.01), and social functioning (<b>P</b> = 0.04), as well as a favorable score in global health status (<b>P</b> = 0.07) than did patients who received HA-cWBRT. There were no differences in physical and role function scales between the two arms over time. The differences were statistically significant and clinically relevant mostly during the early follow-up period (for cognitive functioning at 2 & 4 months, emotional functioning at 2, 9 & 12 months, social functioning at 2 & 4 months, and global health status at 4 months). Correlation analysis showed that cognitive and emotional function scales were highly related (r value = 0.67 at 2 months, 0.85 at 4 months, and 0.68 at 6 months, respectively, all <i>P</i> < 0.001) <h3>Conclusion</h3> In contract to the objective standardized neurocognitive test, patients received hippocampal-avoidant WBRT for brain metastases reported worse HRQOL in cognitive, emotional and social functioning over time. There as a strong correlation between cognitive and emotional functioning. Further investigation on the emotional outcomes after WBRT is warrant.