The Effects of Sequential Treatments on Hippocampal Volume in Malignant Glioma Patients

Objectives: Malignant gliomas (MG) are very aggressive tumors. Patients receive multi-modal therapies such as surgery, radiation and chemotherapy [temozolomide (Temodar or TMZ) followed in many cases by bevacizumab (Avastin)] to improve their likelihood of survival. The survivors are affected by multiple learning and memory deficits referred to as cancer-related cognitive impairment (CRCI). Greater deterioration over time in hippocampal specific cognitive tasks was shown in patients receiving bevacizumab in addition to radiation and temozolomide for a longer period of time (RTOG 0825). However the rate of hippocampal atrophy following treatment using these multi-modal therapies has not yet been determined. The goal of this study is to determine the rate of hippocampal atrophy in patients treated with radiation and temozolomide followed by bevacizumab. Methods: We used the serial MRIs obtained as parts of standard clinical care in patients with MG. Measurements were done using the Medical Image Processing, Analysis and Visualization (MIPAV) software. The hippocampus in the contralateral hemisphere was manually traced and measured, to avoid morphological structure changes induced by the tumor, radiation fields or surgical markers.Results: Retrospective analysis of 13 patients being treated for recurrent brain tumor revealed a longitudinal progression of hippocampal atrophy, with a maximum volume loss of 33.3% for patients on treatment for up to 5 years. There was no detectable hippocampal atrophy during the chemo-radiation followed by adjuvant temozolomide. A significant decrease in the absolute hippocampus volume was noted after 6 months of continuous bevacizumab treatment (p<0.05) and progressed over the next three years. Our overall rate of hippocampal atrophy is higher than the one previously reported in Alzheimer disease patients.Conclusions: The loss of hippocampal volume is minimal during the first months after diagnosis, when the patients receive chemo-radiation and adjuvant temozolomide. However, prolonged treatment and bevacizumab is associated with a significant rate of hippocampal volume loss