title: The effects of sequential treatments on hippocampal volumes in malignant glioma patients.
abstract: Malignant gliomas (MG) are very aggressive tumors. In an effort to improve the outcome, the patients receive multi-modal therapies such as surgery, radiation and chemotherapy (temozolomide followed in many cases by bevacizumab). The survivors are affected by multiple learning and memory deficits. 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). The rate of hippocampal atrophy in patients treated with radiation and temozolomide followed by bevacizumab is not yet determined, and is the goal of the present study. 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. We determined a longitudinal progression of hippocampal atrophy-with the maximum volume loss (33.26 %) for the patients that were on treatment for 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). The hippocampal volume loss progressed over the next 3 years, and was higher than the one previously reported in Alzheimer disease patients. The hippocampal volume loss is minimal during the 1 month after diagnosis, when the patients receive chemo-radiation and adjuvant temozolomide. However, prolonged treatment including bevacizumab is associated with a significant rate of hippocampal volume loss.
authors.affiliation: Department of Neurology, UC Irvine Medical Center, 200 S. Manchester Avenue, Suite 206, Orange, CA, 92868, USA.
authors.forename: Shantell C
authors.initials: SC
authors.lastname: Nolen
authors.affiliation: Department of Neurology, UC Irvine Medical Center, 200 S. Manchester Avenue, Suite 206, Orange, CA, 92868, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Neurology, UC Irvine Medical Center, 200 S. Manchester Avenue, Suite 206, Orange, CA, 92868, USA.
authors.forename: Shruti
authors.initials: S
authors.lastname: Shantharam
authors.affiliation: Department of Radiology, UC Irvine Medical Center, Orange, USA.
authors.forename: Hon J
authors.initials: HJ
authors.lastname: Yu
authors.affiliation: Department of Radiology, UC Irvine Medical Center, Orange, USA.|Chao Family Comprehensive Cancer Center, UC Irvine Medical Center, Orange, USA.
authors.forename: Lydia
authors.initials: L
authors.lastname: Su
authors.affiliation: Health Policy Research Institute, Orange, USA.|Department of Family Medicine, UC Irvine Medical Center, Orange, USA.
authors.forename: John
authors.initials: J
authors.lastname: Billimek
authors.affiliation: Department of Neurology, UC Irvine Medical Center, 200 S. Manchester Avenue, Suite 206, Orange, CA, 92868, USA. dbota@uci.edu.|Chao Family Comprehensive Cancer Center, UC Irvine Medical Center, Orange, USA. dbota@uci.edu.|Department of Neurological Surgery, UC Irvine Medical Center, Orange, USA. dbota@uci.edu.
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Bota
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001284:Atrophy / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D000068258:Bevacizumab / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy / Q000379:methods; D012189:Retrospective Studies; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000068258:Bevacizumab; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Bevacizumab; Hippocampus; Malignant glioma; Radiation; Temozolomide