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Radio-pathomic maps of glioblastoma identify phenotypes of non-enhancing tumor infiltration associated with bevacizumab treatment response. J Neurooncol 2024 Apr;167(2):233-241



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Pubmed Central ID




Scopus ID

2-s2.0-85185314152 (requires institutional sign-in at Scopus site)


BACKGROUND: Autopsy-based radio-pathomic maps of glioma pathology have shown substantial promise inidentifying areas of non-enhancing tumor presence, which may be able to differentiate subsets of patients that respond favorably to treatments such as bevacizumab that have shown mixed efficacy evidence. We tested the hypthesis that phenotypes of non-enhancing tumor fronts can distinguish between glioblastoma patients that will respond favorably to bevacizumab and will visually capture treatment response.

METHODS: T1, T1C, FLAIR, and ADC images were used to generate radio-pathomic maps of tumor characteristics for 79 pre-treatment patients with a primary GBM or high-grade IDH1-mutant astrocytoma for this study. Novel phenotyping (hypercellular, hypocellular, hybrid, or well-circumscribed front) of the non-enhancing tumor front was performed on each case. Kaplan Meier analyses were then used to assess differences in survival and bevacizumab efficacy between phenotypes. Phenotype compartment segmentations generated longitudinally for a subset of 26 patients over the course of bevacizumab treatment, where a mixed effect model was used to detect longitudinal changes.

RESULTS: Well-Circumscribed patients showed significant/trending increases in survival compared to Hypercellular Front (HR = 2.0, p = 0.05), Hypocellular Front (HR = 2.02, p = 0.03), and Hybrid Front tumors (HR = 1.75, p = 0.09). Only patients with hypocellular or hybrid fronts showed significant survival benefits from bevacizumab treatment (HR = 2.35, p = 0.02; and HR = 2.45, p = 0.03, respectively). Hypocellular volumes decreased by an average 50.52 mm3 per day of bevacizumab treatment (p = 0.002).

CONCLUSION: Patients with a hypocellular tumor front identified by radio-pathomic maps showed improved treatment efficacy when treated with bevacizumab, and reducing hypocellular volumes over the course of treatment may indicate treatment response.

Author List

Bobholz SA, Hoefs A, Hamburger J, Lowman AK, Winiarz A, Duenweg SR, Kyereme F, Connelly J, Coss D, Krucoff M, Banerjee A, LaViolette PS


Anjishnu Banerjee PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Jennifer M. Connelly MD Professor in the Neurology department at Medical College of Wisconsin
Max O. Krucoff MD Assistant Professor in the Neurosurgery department at Medical College of Wisconsin
Peter LaViolette PhD Professor in the Radiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiogenesis Inhibitors
Antibodies, Monoclonal, Humanized
Brain Neoplasms
Magnetic Resonance Imaging
Neoplasm Recurrence, Local