title: Early perfusion MRI predicts survival outcome in patients with recurrent glioblastoma treated with bevacizumab and carboplatin.
abstract: Bevacizumab, an anti-angiogenic agent, is FDA-approved for use in patients with recurrent glioblastoma multiforme (rGBM). The radiologic evaluation of tumor response to bevacizumab is complex and there is no validated method of monitoring tumor vascularity during therapy. We evaluated perfusion-weighted MR imaging (PWI) in our cohort of patients enrolled in the CABARET trial, which examined the effectiveness of bevacizumab with or without carboplatin in patients with rGBM. Pre-treatment and early follow-up (4- and 8-week) PWI were used to calculate relative cerebral blood volume (rCBV) histogram statistics of the contrast-enhancing and FLAIR hyperintense tumor volumes. A novel rCBV measurement (load) was developed to estimate the total volume of perfused tumor blood vessels. Changes in all rCBV measures were examined for correlations with progression-free (PFS) and overall survival (OS). All of our 15 patients enrolled in the CABARET trial were included. Median PFS and OS were 23 and 45 weeks respectively. Kaplan-Meier analysis of pre-treatment PWI revealed an 18 week reduction in median OS in patients with high tumor rCBV (p = 0.031). Changes in rCBV measures, especially load, correlated significantly with PFS and OS at both follow-up time-points. Patients with the greatest reduction in rCBVloadby 8-weeks of therapy had a significantly increased median OS (30 weeks; p = 0.013). PWI may be of significant clinical utility in managing patients with rGBM, particularly those treated with anti-angiogenic agents such as bevacizumab. These findings need to be confirmed prospectively in larger studies.
authors.affiliation: Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, 6th Floor, Clinical Sciences Building, Royal Parade, Parkville, VIC, 3050, Australia.
authors.forename: Iwan E
authors.initials: IE
authors.lastname: Bennett
authors.affiliation: Department of Medical Oncology, The Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3050, Australia.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Field
authors.affiliation: Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, 6th Floor, Clinical Sciences Building, Royal Parade, Parkville, VIC, 3050, Australia.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hovens
authors.affiliation: Department of Radiology, The Royal Melbourne Hospital, The University of Melbourne, 1st Floor, 300 Grattan St, Parkville, VIC, 3050, Australia.
authors.forename: Bradford A
authors.initials: BA
authors.lastname: Moffat
authors.affiliation: Department of Medical Oncology, The Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3050, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rosenthal
authors.affiliation: Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, 6th Floor, Clinical Sciences Building, Royal Parade, Parkville, VIC, 3050, Australia.|Department of Neurosurgery, The Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3050, Australia.
authors.forename: Katharine
authors.initials: K
authors.lastname: Drummond
authors.affiliation: Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, 6th Floor, Clinical Sciences Building, Royal Parade, Parkville, VIC, 3050, Australia.|Department of Neurosurgery, The Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3050, Australia.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Kaye
authors.affiliation: Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, 6th Floor, Clinical Sciences Building, Royal Parade, Parkville, VIC, 3050, Australia. morokoff@unimelb.edu.au.|Department of Neurosurgery, The Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3050, Australia. morokoff@unimelb.edu.au.
authors.forename: Andrew P
authors.identifier: 0000-0002-5159-3438
authors.initials: AP
authors.lastname: Morokoff
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D016190:Carboplatin / Q000627:therapeutic use*; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000074322:Antineoplastic Agents, Immunological; D000068258:Bevacizumab; D016190:Carboplatin
keywords: Bevacizumab; DSC; Glioblastoma; MRI; Perfusion; rCBV