Progressing Bevacizumab-Induced Diffusion Restriction Is Associated with Coagulative Necrosis Surrounded by Viable Tumor and Decreased Overall Survival in Patients with Recurrent Glioblastoma. AJNR Am J Neuroradiol 2016 Dec;37(12):2201-2208
Date
08/06/2016Pubmed ID
27492073Pubmed Central ID
PMC5161572DOI
10.3174/ajnr.A4898Scopus ID
2-s2.0-85006469905 (requires institutional sign-in at Scopus site) 55 CitationsAbstract
BACKGROUND AND PURPOSE: Patients with recurrent glioblastoma often exhibit regions of diffusion restriction following the initiation of bevacizumab therapy. Studies suggest that these regions represent either diffusion-restricted necrosis or hypercellular tumor. This study explored postmortem brain specimens and a population analysis of overall survival to determine the identity and implications of such lesions.
MATERIALS AND METHODS: Postmortem examinations were performed on 6 patients with recurrent glioblastoma on bevacizumab with progressively growing regions of diffusion restriction. ADC values were extracted from regions of both hypercellular tumor and necrosis. A receiver operating characteristic analysis was performed to define optimal ADC thresholds for differentiating tissue types. A retrospective population study was also performed comparing the overall survival of 64 patients with recurrent glioblastoma treated with bevacizumab. Patients were separated into 3 groups: no diffusion restriction, diffusion restriction that appeared and progressed within 5 months of bevacizumab initiation, and delayed or stable diffusion restriction. An additional analysis was performed assessing tumor O6-methylguanine-DNA-methyltransferase methylation.
RESULTS: The optimal ADC threshold for differentiation of hypercellularity and necrosis was 0.736 × 10-3mm2/s. Progressively expanding diffusion restriction was pathologically confirmed to be coagulative necrosis surrounded by viable tumor. Progressive lesions were associated with the worst overall survival, while stable lesions showed the greatest overall survival (P < .05). Of the 40% of patients with O6-methylguanine-DNA-methyltransferase methylated tumors, none developed diffusion-restricted lesions.
CONCLUSIONS: Progressive diffusion-restricted lesions were pathologically confirmed to be coagulative necrosis surrounded by viable tumor and associated with decreased overall survival. Stable lesions were, however, associated with increased overall survival. All lesions were associated with O6-methylguanine-DNA-methyltransferase unmethylated tumors.
Author List
Nguyen HS, Milbach N, Hurrell SL, Cochran E, Connelly J, Bovi JA, Schultz CJ, Mueller WM, Rand SD, Schmainda KM, LaViolette PSAuthors
Elizabeth J. Cochran MD Adjunct Professor in the Pathology department at Medical College of WisconsinJennifer M. Connelly MD Professor in the Neurology department at Medical College of Wisconsin
Peter LaViolette PhD Professor in the Radiology department at Medical College of Wisconsin
Wade M. Mueller MD Professor in the Neurosurgery department at Medical College of Wisconsin
Kathleen M. Schmainda PhD Professor in the Biophysics department at Medical College of Wisconsin
Christopher J. Schultz MD Chair, Professor in the Radiation Oncology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdultAged
Antineoplastic Agents
Bevacizumab
Brain Neoplasms
Diffusion Magnetic Resonance Imaging
Female
Glioblastoma
Humans
Male
Middle Aged
Necrosis
Neoplasm Recurrence, Local
Retrospective Studies
