Wendland, Merideth M

Abstract Background This study evaluated the association between health-related quality of life (HRQOL) and cognition in patients receiving memantine for prevention of cognitive dysfunction during whole-brain radiotherapy (WBRT). Methods Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine, 20 mg per day, within 3 days of initiating radiotherapy, for 24 weeks. The Functional Assessment of Cancer Therapy-Brain module (FACT-Br) and Medical Outcomes Scale-Cognitive Functioning Scale (MOS-C) were completed in coordination with serial standardized tests of cognitive function. Results Of the 508 eligible patients, 442 (87%) consented to participate in the HRQOL portion and contributed to baseline analyses. Evaluable patients at 24 weeks (n = 246) included surviving patients completing FACT-Br, MOS-C, and objective cognitive assessments (n = 146, 59%) and patients alive at time of missed assessment (n = 100, 41%). Baseline cognitive function correlated significantly with FACT-Br and MOS-C self-reports. All domains of objective cognitive function showed declines over time. Neither FACT-Br nor MOS-C differed between the treatment arms. Emotional and functional well-being subscales of the FACT improved over time while the remainder of the FACT-Br domains remained stable. MOS-C scores declined over time. Conclusion Baseline cognitive function correlated significantly with FACT-Br and MOS-C scores. No by-arm differences in HRQOL were observed despite differences in objective cognitive function. Patient attrition and poor testing compliance remain significant problems in studies of cognitive function of brain metastases patients and further effort is needed to improve compliance with testing and sensitivity of patient-reported measures.

Abstract BACKGROUND The influence of subtotal resection (STR) on neurocognitive function (NCF), quality of life, and symptom burden in glioblastoma is unknown. If bevacizumab preferentially benefits patients with STR is unknown. OBJECTIVE To examine these uncertainties. METHODS NCF and patient reported outcomes (PRO) were prospectively collected in NRG Oncology RTOG 0525 and 0825. Changes in NCF and PRO measures from baseline to prespecified times were examined by Wilcoxon test, and mixed effects longitudinal modeling, to assess differences between patients who received STR vs gross-total resection. Changes were also compared among STR patients on 0825 receiving placebo vs bevacizumab to assess for a preferential therapeutic effect. Overall survival between STR and gross-total resection patients was compared using the Kaplan–Meier method. RESULTS A total of 427 patients were eligible with STR present in 37%. At baseline, patients with STR had worse NCF, worse MD Anderson Symptom Inventory Brain Tumor Neurological Factor ratings ( P = .004), and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire ( P = .002). Longitudinal multivariate analysis associated STR with worse NCF (Hopkins Verbal Learning Test–Revised Delayed Recognition [ P = .048], Trail Making Test Part A [ P = .035], and Controlled Oral Word Association [ P = .049]). One hundred eighty-three STR patients from 0825 were analyzed (89 bevacizumab, 94 placebo); bevacizumab failed to demonstrate improvement in select NCF or PRO measures. CONCLUSION STR patients had worse NCF and PROs before therapy. During adjuvant therapy, STR patients had worse objective NCF, despite accounting for tumor location. STR did not result in a detriment to OS. The addition of bevacizumab did not preferentially improve PRO or NCF outcomes in STR patients.