The relationship between the degree of brain edema regression and changes in cognitive function in patients with recurrent glioma treated with bevacizumab and temozolomide

Background: This retrospective study aims to assess the impacts on cognitive status and quality of life in recurrent high-grade glioma patients treated with temozolomide (TMZ), either alone or in combination with bevacizumab (BEV), and explore the relationship between the brain edema regression, BEV use, and cognitive status. Methods: A total of 125 patients with recurrent high-grade glioma were enrolled in this study, of which 65 patients were treated with BEV (5-10 mg/kg IV every 2 weeks) plus TMZ (200 mg/m(2) every 28 days, d1-5), and 60 patients were treated with TMZ (200 mg/m(2) every 28 days, d1-5) alone. The treatment response was evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria. Tumor-associated edema was evaluated with T2WI magnetic resonance imaging (MRI) and quantitative T2 mapping sequence, and an Edema Regression Index was designed to quantify volumetric changes in edema imaging after every treatment cycle. Cognitive intelligence state and quality of life were evaluated using the Mini-Mental State Examination (MMSE) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30). Results: Radiologically, the partial response rate was 78.5% in the BEV + TMZ group and 38.3% in the TMZ group. After the first cycle of treatment, the mean score of the MMSE was 21.1 +/- 2.0 and 24.1 +/- 1.4 (P<0.001) in the TMZ group and the BEV + TMZ group, respectively. In the functioning domains of the QLQ-C30, scales of physical functioning, emotional functioning and cognitive functioning were 43.0 +/- 7.0 vs. 61.7 +/- 12.5 (P<0.001), 44.5 +/- 8.8 vs. 63.4 +/- 6.9 (P<0.001) and 42.4 +/- 8.8 vs. 63.7 +/- 12.0 (P<0.001) in the TMZ group and the BEV + TMZ group, respectively. In the BEV + TMZ group, a correlation between the Edema Regression Index and improvement in cognitive status and quality of life was observed. Patients with Edema Regression Index scores higher than 50% gained a 25.6% increase in the mean MMSE score from 19.9 +/- 1.6 to 25.0 +/- 1.1 (P<0.001). In the BEV + TMZ group, physical functioning, emotional functioning, and cognitive functioning increased by 76.8%, 53.1%, and 81.5%, respectively, while scores of nausea/vomiting decreased by 40.3% to 32.1. Patients with no evident edema observed in the pre-BEV MRI scans were given a prolonged four-cycle course of BEV. No significant improvement was observed in the MMSE score and the QLQ score with additional cycles of BEV. Conclusions: A close relationship was observed between Edema Regression Index and a change in cognitive function in patients treated with BEV and TMZ. Compared with TMZ alone, the combination of TMZ and BEV could improve the cognitive function and quality of life of patients with recurrent high-grade gliomas. The Edema Regression Index could be used as a surrogate imaging biomarker to predict patients who may or may not gain cognitive benefit from the combination therapy of TMZ and BEV, which warrants further prospective clinical studies for validation.